Biomarkers for predicting clinical response of cancer patients to treatment with immunotherapeutic agent

ABSTRACT

Provided herein are prognostic and diagnostic methods for predicting likelihood of clinical response of a subject having cancer to treatment with an immunotherapeutic agent. Also provided herein are methods for treating a subject having cancer with an immunotherapeutic agent after determining likelihood of clinical response of the subject to such treatment.

BACKGROUND

The National Cancer Institute has estimated that in the United States alone, 1 in 3 people will be struck with cancer during their lifetime. Moreover, approximately 50% to 60% of people contracting cancer will eventually succumb to the disease. The widespread occurrence of this disease underscores the need for improved anticancer regimens for the treatment of malignancy.

Due to the wide variety of cancers presently observed, numerous anticancer agents have been developed to destroy cancer within the body. These compounds are administered to cancer patients with the objective of destroying or otherwise inhibiting the growth of malignant cells while leaving normal, healthy cells undisturbed. Anticancer agents have been classified based upon their mechanism of action, and are often referred to as chemotherapeutics or immunotherapeutics (agents whose therapeutic effects are mediated by their immuno-modulating properties). The vertebrate immune system requires multiple signals to achieve optimal immune activation; see, e.g., Janeway, Cold Spring Harbor Symp. Quant. Biol., 54:1-14 (1989); and Paul, W. E., ed., Fundamental Immunology, 4th Edition, Raven Press, NY (1998), particularly Chapters 12 and 13, pp. 411-478. Interactions between T lymphocytes (T cells) and antigen presenting cells (APCs) are essential to the immune response. Levels of many cohesive molecules found on T cells and APC's increase during an immune response (Springer et al., Ann. Rev. Immunol., 5:223-252 (1987); Shaw et al., Curr. Opin. Immunol., 1:92-97 (1988); and Hemler, Immunology Today, 9:109-113 (1988)). Increased levels of these molecules may help explain why activated APCs are more effective at stimulating antigen-specific T cell proliferation than are resting APCs (Kaiuchi et al., J. Immunol., 131:109-114 (1983); Kreiger et al., J. Immunol., 135:2937-2945 (1985); McKenzie, J. Immunol., 141:2907-2911 (1988); and Hawrylowicz et al., J. Immunol., 141:4083-4088 (1988)).

T cell immune response is a complex process that involves cell-cell interactions (Springer et al., Ann. Rev. Immunol., 5:223-252 (1987)), particularly between T and accessory cells such as APCs, and production of soluble immune mediators (cytokines or lymphokines) (Dinarello, New Engl. J. Med., 317:940-945 (1987); and Sallusto, J. Exp. Med., 179:1109-1118 (1997)). This response is regulated by several T-cell surface receptors, including the T-cell receptor complex (Weiss, Ann. Rev. Immunol., 4:593-619 (1986)) and other “accessory” surface molecules (Allison, Curr. Opin. Immunol., 6:414-419 (1994); Springer (1987), supra). Many of these accessory molecules are naturally occurring cell surface differentiation (CD) antigens defined by the reactivity of monoclonal antibodies on the surface of cells (McMichael, ed., Leukocyte Typing Iff, Oxford Univ. Press, Oxford, N.Y. (1987)).

Early studies suggested that B lymphocyte activation requires two signals (Bretscher, Science, 169:1042-1049 (1970)) and now it is believed that all lymphocytes require two signals for their optimal activation, an antigen specific or clonal signal, as well as a second, antigen non-specific signal. (Janeway, supra). Freeman (J. Immunol., 143:2714-2722 (1989)) isolated and sequenced a cDNA clone encoding a B cell activation antigen recognized by MAb B7 (Freeman, J. Immunol., 139:3260 (1987)). COS cells transfected with this cDNA have been shown to stain by both labeled MAb B7 and MAb BB-1 (Clark, Human Immunol., 16:100-113 (1986); Yokochi, J. Immunol., 128:823 (1981); Freeman et al. (1989), supra; and Freeman et al. (1987), supra). In addition, expression of this antigen has been detected on cells of other lineages, such as monocytes (Freeman et al., (1989) supra).

T helper cell (Th) antigenic response requires signals provided by APCs. The first signal is initiated by interaction of the T cell receptor complex (Weiss, J. Clin. Invest., 86:1015 (1990)) with antigen presented in the context of major histocompatibility complex (MHC) molecules on the APC (Allen, Immunol. Today, 8:270 (1987)). This antigen-specific signal is not sufficient to generate a full response, and in the absence of a second signal may actually lead to clonal inactivation or anergy (Schwartz, Science, 248:1349 (1990)). The requirement for a second “costimulatory” signal has been demonstrated in a number of experimental systems (Schwartz, supra; Weaver et al., Immunol. Today, 11:49 (1990)).

CD28 antigen, a homodimeric glycoprotein of the immunoglobulin superfamily (Aruffo et al., Proc. Natl. Acad. Sci., 84:8573-8577 (1987)), is an accessory molecule found on most mature human T cells (Damle et al., J. Immunol., 131:2296-2300 (1983)). Current evidence suggests that this molecule functions in an alternative T cell activation pathway distinct from that initiated by the T-cell receptor complex (June et al., Mol. Cell. Biol., 7:4472-4481 (1987)). Some studies have indicated that CD28 is a counter-receptor for the B cell activation antigen, B7/BB-1 (Linsley et al., Proc. Natl. Acad. Sci. USA, 87:5031-5035 (1990)). The B7 ligands are also members of the immunoglobulin superfamily but have, in contrast to CD28, two Ig domains in their extracellular region, an N-terminal variable (V)-like domain followed by a constant (C)-like domain.

Delivery of a non-specific costimulatory signal to the T cell requires at least two homologous B7 family members found on APCs, B7-1 (also called B7, B7. 1, or CD80) and B7-2 (also called B7.2 or CD86), both of which can deliver costimulatory signals to T cells via CD28. Costimulation through CD28 promotes T cell activation.

CD28 has a single extracellular variable region (V)-like domain (Aruffo et al., supra). A homologous molecule, CTLA-4, has been identified by differential screening of a murine cytolytic-T cell cDNA library (Brunet, Nature, 328:267-270 (1987)). CTLA-4 (CD152) is a T cell surface molecule and also a member of the immunoglobulin (Ig) superfamily, comprising a single extracellular Ig domain. Researchers have reported the cloning and mapping of a gene for the human counterpart of CTLA-4 (Dariavach et al., Eur. J. Immunol., 18:1901-1905 (1988)) to the same chromosomal region (2q33-34) as CD28 (Lafage-Pochitaloff et al., Immunogenetics, 31:198-201 (1990)). Sequence comparison between this human CTLA-4 and CD28 proteins reveals significant homology of sequence, with the greatest degree of homology in the juxtamembrane and cytoplasmic regions (Brunet et al. (1988), supra; Dariavach et al. (1988), supra).

The CTLA-4 is inducibly expressed by T cells. It binds to the B7-family of molecules (primarily CD80 and CD86) on APCs (Chambers et al., Ann. Rev. Immunol., 19:565-594 (2001)). When triggered, it inhibits T-cell proliferation and function. Mice genetically deficient in CTLA-4 develop lymphoproliferative disease and autoimmunity (Tivol et al., Immunity, 3:541-547 (1995)). In pre-clinical models, CTLA-4 blockade also augments anti-tumor immunity (Leach et al., Science, 271:1734-1736 (1996); and van Elsas et al., J. Exp. Med., 190:355-366 (1999)). These findings led to the development of antibodies that block CTLA-4 for use in cancer immunotherapy.

Blockade of CTLA-4 by a monoclonal antibody leads to the expansion of all T cell populations, with activated CD4⁺ and CD8⁺ T cells mediating tumor cell destruction (Melero et al., Nat. Rev. Cancer, 7:95-106 (2007); and Wolchok et al., The Oncologist, 13 (Suppl. 4):2-9 (2008)). The antitumor response that results from the administration of anti-CTLA-4 antibodies is believed to be due to an increase in the ratio of effector T cells to regulatory T cells within the tumor microenvironment, rather than simply from changes in T cell populations in the peripheral blood (Quezada et al., J. Clin. Invest., 116:1935-1945 (2006)). One such agent is ipilimumab.

Ipilimumab (previously MDX-010; Medarex Inc., marketed by Bristol-Myers Squibb as YERVOY™) is a fully human anti-human CTLA-4 monoclonal antibody that blocks the binding of CTLA-4 to CD80 and CD86 expressed on antigen presenting cells, thereby, blocking the negative down-regulation of the immune responses elicited by the interaction of these molecules. Initial studies in patients with melanoma showed that ipilimumab could cause objective durable tumor regressions (Phan et al., Proc. Natl. Acad. Sci. USA, 100:8372-8377 (2003)). Also, reductions of serum tumor markers such as CA125 and PSA were seen for some patients with ovarian or prostate cancer, respectively (Hodi et al., Proc. Natl. Acad. Sci. USA, 100:4712-4717 (2003)). Ipilimumab has demonstrated antitumor activity in patients with advanced melanoma (Weber et al., J. Clin. Oncol., 26:5950-5956 (2008); Weber, Cancer Immunol. Immunother., 58:823-830 (2009)). In addition, in a number of phase II and two phase III clinical trials, ipilimumab was shown to increase the overall survival in advanced melanoma patients (Hodi, F. S. et al., “Improved survival with ipilimumab in patients with metastatic melanoma”, New Engl. J. Med., 363:711-723 (2010), and Robert, C. et al., “Ipilimumab plus dacarbazine for previously untreated metastatic melanoma”, New Engl. J. Med., 364:2517-2526 (2011)). Treatment with ipilimumab, however, can result in adverse events in some patients and individual survival outcome may be different.

Provided herein are biomarkers that may be used to predict clinical response of patients to treatment with an immunotherapeutic agent, for example, an anti-CTLA4 antibody such as ipilimumab, prior to receiving the agent, and methods of using the biomarkers for treatment with the immunotherapeutic agent, or for predicting clinical response of a patient treated with the immunotherapeutic agent.

SUMMARY

Provided herein are methods for treating a subject having cancer with an immunotherapeutic agent, comprising (a) determining expression level of at least one gene in a blood sample obtained from the subject, wherein the at least one gene is selected from a first group of genes as listed in Table 2 and a second group of genes as listed in Table 3; (b) determining likelihood of clinical response of the subject to the treatment based on the expression level of the at least one gene in the blood sample, wherein the expression level of the at least one gene selected from the first group of genes is positively correlated with the likelihood of clinical response, and wherein the expression level of the at least one gene selected from the second group of genes is negatively correlated with the likelihood of clinical response; and (c) administering to the subject a therapeutically effective amount of the immunotherapeutic agent for treating the cancer.

Also provided herein are methods for predicting likelihood of clinical response of a subject having cancer to treatment with an immunotherapeutic agent, comprising (a) obtaining a blood sample from the subject before the treatment, (b) determining expression level of at least one gene in the blood sample, wherein the at least one gene is selected from a first group of genes as listed in Table 2 and a second group of genes as listed in Table 3; (c) determining likelihood of clinical response to the treatment based on the expression level of the at least one gene in the blood sample, wherein the expression level of the at least one gene selected from the first group of genes is positively correlated with the likelihood of clinical response, and wherein the expression level of the at least one gene selected from the second group of genes is negatively correlated with the likelihood of clinical response.

Also provided herein are methods for determining whether to treat a subject having cancer with a immunotherapeutic agent, comprising (a) obtaining a blood sample from the subject, (b) determining expression level of at least one gene in a blood sample obtained from the subject, wherein the at least one gene is selected from a first group of genes as listed in Table 2 and a second group of genes as listed in Table 3; (c) determining likelihood of clinical response to the treatment based on the expression level of the at least one gene in the blood sample, wherein the expression level of the at least one gene selected from the first group of genes is positively correlated with the likelihood of clinical response, and wherein the expression level of the at least one gene selected from the second group of genes is negatively correlated with the likelihood of clinical response; and (d) determining whether to treat the subject having cancer with the immunotherapeutic agent based on the likelihood of clinical response.

Also provided herein are methods for treating a subject having cancer with an immunotherapeutic agent, comprising (a) determining expression levels of a first gene and a second gene in a blood sample obtained from the subject, wherein the first gene is IL2RB and a second gene is selected from ASGR1 and ASGR2; (b) determining likelihood of longer overall survival of the subject following the treatment based on the expression levels of the first gene and the second gene in the blood sample, wherein the expression levels of the first gene and the second gene are used to calculate a score according to formula:

Score=−C ₁ *X _(first gene) +C ₂ *X _(second gene),

wherein X_(first gene) and X_(second gene) are normalized mRNA expression levels of the first and the second gene, respectively, and C1 and C2 are each, independently, a number ranging from 0.01 to 3, wherein the score is negatively correlated with the likelihood of longer overall survival; and (c) administering to the subject a therapeutically effective amount of the immunotherapeutic agent for treating the cancer.

Also provided herein are methods for predicting likelihood of longer overall survival of a subject having cancer following treatment with an immunotherapeutic agent, comprising: (a) obtaining a blood sample from the subject before the treatment; (b) determining expression levels of a first gene and a second gene in the blood sample obtained from the subject, wherein the first gene is IL2RB and a second gene is selected from ASGR1 and ASGR2; and (c) determining likelihood of longer overall survival of the subject following the treatment based on the expression levels of the first gene and the second gene in the blood sample, wherein the expression levels of the first gene and the second gene are used to calculate a score according to formula:

Score=−C ₁ *X _(first gene) +C ₂ *X _(second gene),

wherein X_(first gene) and X_(second gene) are normalized mRNA expression levels of the first and the second gene, respectively, and C1 and C2 are each, independently, a number ranging from 0.01 to 3, wherein the score is negatively correlated with the likelihood of longer overall survival.

Also provided herein are methods for determining whether to treat a subject having cancer with a immunotherapeutic agent, comprising: (a) obtaining a blood sample from the subject; (b) determining expression levels of a first gene and a second gene in the blood sample obtained from the subject, wherein the first gene is IL2RB and a second gene is selected from ASGR1 and ASGR2; and (c) determining likelihood of longer overall survival of the subject following the treatment based on the expression levels of the first gene and the second gene in the blood sample, wherein the expression levels of the first gene and the second gene are used to calculate a score according to formula:

Score=−C ₁ *X _(first gene) +C ₂ *X _(second gene),

wherein X_(first gene) and X_(second gene) are normalized mRNA expression levels of the first and the second gene, respectively, and C1 and C2 are each, independently, a number ranging from 0.01 to 3, wherein the score is negatively correlated with the likelihood of longer overall survival; and (d) determining whether to treat the subject with the immunotherapeutic agent based on the likelihood of longer overall survival.

Also provided herein are kits for use for the methods disclosed herein. The kits may comprise one or more reagents for determining expression level of at least one gene in a blood sample, wherein the at least one gene is selected from a first group of genes as listed in Table 2 and a second group of genes as listed in Table 3.

Also provided herein are kits for use for the methods disclosed herein. The kits may comprise one or more reagents for determining expression levels of a first gene and a second gene in a blood sample, wherein the first gene is IL2RB and a second gene is selected from ASGR1 and ASGR2.

TABLE 2 First group of genes IL2RB PMS2L11 CCND3 KLRK1 ZMYND11 TRATRD G3BP TTC17 ZAP70 PPP1R16B CLDN15 ADA CLIC3 TBX21 LOC130074 PRF1 LUC7L2 GFOD1 SPON2 CAT HLA-A/// HLA-H/// LOC642047 /// LOC649853 /// LOC649864 HOP IMP3 CECR7 GNLY CD2 C7ORF24 TMEM161A GZMA ZNF364 PRKCH SPCS2 ID2 RUNX3 RPA2 KLRD1 GZMB SLC25A5 SH2D2A CCND2 CHST12 MATK NKG7 MNAB CDC25B ARL2BP GPR56 GIMAP4 CCL4 TXNIP EOMES

TABLE 3 Second group of genes ASGR1 ING2 TSPO ASGR2 HOMER3 SERTAD3 CENTA2 RAB31 SULT1A1 PGLS ARF5 S100A6 CEBPA IL1RN STX10 ZBP1 LILRA5 IFI6 MAPBPIP PYCARD C16ORF68 CEACAM3 HPSE

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1. Kaplan-Meier estimates of overall survival (OS) for patients split into 2 groups based on the two-gene signature (IL2RB+ASGR2): training cohort (Panel A), test cohort (Panel B), and both cohorts pooled (Panel C). IL2RB and ASGR2 were identified by applying two different methods to the training cohort: multivariable Cox PH regression with elastic-net penalties, and unregularized univariate Cox PH regression coupled with evaluation of 2- and 3-gene combinations. Once genes were identified, coefficients were estimated using unregularized Cox PH regression on the training cohort, and a classification threshold was selected. Finally, the selected genes, coefficients, and thresholds were applied to the test cohort and to both cohorts pooled.

FIG. 2. Combining the two-gene signature with prognostic factor baseline LDH in the training cohort (Panel A), test cohort (Panel B), both cohorts pooled (Panel C), and both cohorts pooled using two thresholds (Panel D). Coefficients were estimated using Cox PH regression in the training cohort alone. They were then applied to the training cohort, test cohort, and both cohorts pooled to obtain patient scores. The threshold for panels A-C was determined using threshold optimization in the training cohort alone, then applying this threshold to the training cohort, test cohort, and both cohorts pooled. The two thresholds used in panel D were determined using threshold optimization on both cohorts pooled together. Time-dependent ROC curves at 12 months for the training cohort (Panel E), test cohort (Panel F), and both cohorts pooled (Panel G) are presented for both the two-gene signature (red) and the three-factor signature (black), along with the relevant AUCs. The stars indicate the points on the ROC curve corresponding to the selected thresholds.

FIG. 3. Functional and enrichment analysis yields insights into the biological mechanisms underlying the two-gene signature's association with OS in advanced metastatic melanoma patients receiving ipilimumab. Network analysis of genes (red) correlated with IL2RB (Panel A) suggests a role for EOMES in connecting IL2RB with the genes significantly correlated with it, as well as with CTLA-4 itself. For genes found to be associated with OS (Panel B, row headings) the relative expression of each gene across cell types (Panel B, columns) in the DMAP¹⁸ data is shown in a heat map. This analysis suggests roles for NK and T cells (Panel B, upper left) and B cells (Panel B, middle) in genes positively associated with OS, and a role for myeloid cells (Panel B, lower right) in genes negatively associated with OS. The genes and biological mechanisms (Panel C) suggest that the two-gene signature may represent a balance of anti-tumor lymphocyte-driven functions and pro-tumor myeloid-driven functions.

FIG. 4. Time-dependent ROC curves at 12 months comparing the two-gene signature (IL2RB+ASGR2) (black) with the three-gene signatures (red) (IL2RB+ASGR2+ZBP1), (IL2RB+ASGR2+CAT), and (IL2RB+ASGR2+ASGR1).

FIG. 5. Boxplot summarizing the distribution of normalized expression levels for genes ASGR1, ASGR2, and IL2RB in the training and test cohorts pooled. Mean expression of ASGR2 was 1.54-fold higher than ASGR1, and the difference was significant by a paired t-test (P=1.32×10⁻⁶⁹).

FIG. 6. Kaplan-Meier estimates of OS, and log-rank test p-values, for patients split into 2 groups based on the two-gene signature, IL2RB+ASGR1: training cohort (Panel A), test cohort (Panel B), and both cohorts pooled (Panel C). The results are comparable to those achieved by IL2RB and ASGR2 (FIG. 1).

FIG. 7. Estimation of classification threshold(s) using the log-rank test chi-square statistic for (A) two-gene signature (IL2RB+ASGR2) in training cohort, (B) three-factor signature (IL2RB+ASGR2+LDH) in training cohort, and (C) three-factor signature (IL2RB+ASGR2+LDH) in pooled cohort (two thresholds).

FIG. 8. Analysis of EOMES by qPCR yielded a highly significant Kaplan-Meier plot (log-rank p=6.86×10⁻⁸).

The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.

DETAILED DESCRIPTION

The methods described herein are based on certain gene expression signatures. The gene expression signatures may be used as biomarkers, e.g., prognostic, predictive biomarkers for clinical efficacy and/or safety.

Provided herein are methods for treating a subject having cancer with an immunotherapeutic agent, comprising (a) determining expression level of at least one gene in a blood sample obtained from the subject, wherein the at least one gene is selected from a first group of genes as listed in Table 2 and a second group of genes as listed in Table 3; (b) determining likelihood of clinical response of the subject to the treatment based on the expression level of the at least one gene in the blood sample, wherein the expression level of the at least one gene selected from the first group of genes is positively correlated with the likelihood of clinical response, and wherein the expression level of the at least one gene selected from the second group of genes is negatively correlated with the likelihood of clinical response; and (c) administering to the subject a therapeutically effective amount of the immunotherapeutic agent for treating the cancer.

Also provided herein are methods of predicting likelihood of clinical response of a subject having cancer to treatment with an immunotherapeutic agent, comprising (a) obtaining a blood sample from the subject before the treatment, (b) determining expression level of at least one gene in the blood sample, wherein the at least one gene is selected from a first group of genes as listed in Table 2 and a second group of genes as listed in Table 3; (c) determining likelihood of clinical response of the subject to the treatment based on the expression level of the at least one gene in the blood sample, wherein the expression level of the at least one gene selected from the first group of genes is positively correlated with the likelihood of clinical response, and wherein the expression level of the at least one gene selected from the second group of genes is negatively correlated with the likelihood of clinical response.

Also provided herein are methods for determining whether to treat a subject having cancer with a immunotherapeutic agent, comprising (a) obtaining a blood sample from the subject, (b) determining expression level of at least one gene in a blood sample obtained from the subject, wherein the at least one gene is selected from a first group of genes as listed in Table 2 and a second group of genes as listed in Table 3; (c) determining likelihood of clinical response of the subject to the treatment based on the expression level of the at least one gene in the blood sample, wherein the expression level of the at least one gene selected from the first group of genes is positively correlated with the likelihood of clinical response, and wherein the expression level of the at least one gene selected from the second group of genes is negatively correlated with the likelihood of clinical response; and (d) determining whether to treat the subject with the immunotherapeutic agent based on the likelihood of clinical response.

Also provided herein are methods for treating a subject having cancer with an immunotherapeutic agent, comprising (a) determining expression levels of a first gene and a second gene in a blood sample obtained from the subject, wherein the first gene is IL2RB and a second gene is selected from ASGR1 and ASGR2; (b) determining likelihood of longer overall survival of the subject following the treatment based on the expression levels of the first gene and the second gene in the blood sample, wherein the expression levels of the first gene and the second gene are used to calculate a score according to formula:

Score=−C ₁ *X _(first gene) +C ₂ *X _(second gene),

wherein X_(first gene) and X_(second gene) are normalized mRNA expression levels of the first and the second gene, respectively, and C1 and C2 are each, independently, a number ranging from 0.01 to 3, wherein the score is negatively correlated with the likelihood of longer overall survival; and (c) administering to the subject a therapeutically effective amount of the immunotherapeutic agent for treating the cancer.

Also provided herein are methods of predicting likelihood of longer overall survival of a subject having cancer following treatment with an immunotherapeutic agent, comprising: (a) obtaining a blood sample from the subject before the treatment; (b) determining expression levels of a first gene and a second gene in the blood sample obtained from the subject, wherein the first gene is IL2RB and a second gene is selected from ASGR1 and ASGR2; and (c) determining likelihood of longer overall survival of the subject following the treatment based on the expression levels of the first gene and the second gene in the blood sample, wherein the expression levels of the first gene and the second gene are used to calculate a score according to formula:

Score=−C ₁ *X _(first gene) +C ₂ *X _(second gene),

wherein X_(first gene) and X_(second gene) are normalized mRNA expression levels of the first and the second gene, respectively, and C1 and C2 are each, independently, a number ranging from 0.01 to 3, wherein the score is negatively correlated with the likelihood of longer overall survival.

Also provided herein are methods for determining whether to treat a subject having cancer with a immunotherapeutic agent, comprising: (a) obtaining a blood sample from the subject; (b) determining expression levels of a first gene and a second gene in the blood sample obtained from the subject, wherein the first gene is IL2RB and a second gene is selected from ASGR1 and ASGR2; and (c) determining likelihood of longer overall survival of the subject following the treatment based on the expression levels of the first gene and the second gene in the blood sample, wherein the expression levels of the first gene and the second gene are used to calculate a score according to formula:

Score=−C ₁ *X _(first gene) +C ₂ *X _(second gene),

wherein X_(first gene) and X_(second gene) are normalized mRNA expression levels of the first and the second gene, respectively, and C1 and C2 are each, independently, a number ranging from 0.01 to 3, wherein the score is negatively correlated with the likelihood of longer overall survival; and (d) determining whether to treat the subject with the immunotherapeutic agent based on the likelihood of longer overall survival.

Also provided herein are kits for use for the methods disclosed herein. The kits may comprise one or more reagents for determining expression level of at least one gene in a blood sample, wherein the at least one gene is selected from a first group of genes as listed in Table 2 and a second group of genes as listed in Table 3.

Also provided herein are kits for use for the methods disclosed herein. The kits may comprise one or more reagents for determining expression levels of a first gene and a second gene in a blood sample, wherein the first gene is IL2RB and a second gene is selected from ASGR1 and ASGR2.

The term “treating” or “treatment” refers to administering an immunotherapeutic agent described herein to a subject that has cancer, or has a symptom of cancer, or has a predisposition toward cancer, with the purpose to cure, heal, alleviate, relieve, alter, remedy, ameliorate, improve, or affect cancer, the symptoms of cancer, or the predisposition toward cancer.

The terms “patient” or “subject” are used interchangeably and refer to mammals such as human patients and non-human primates, as well as experimental animals such as rabbits, rats, and mice, and other animals. Animals include all vertebrates, e.g., mammals and non-mammals, such as sheep, dogs, cows, chickens, amphibians, and reptiles.

The term “immunotherapeutic agent” means an agent that may enhance or alter immune response to a disease or disorder such as cancer. The term “immune response” refers to the concerted action of immune cells, including lymphocytes, antigen presenting cells, phagocytic cells, and granulocytes, and soluble macromolecules produced by the above cells or the liver (including antibodies, cytokines, and complement), that results in selective damage to, destruction of, or elimination from the human body of invading pathogens, cells or tissues infected with pathogens, or cancerous cells. An immunotherapeutic agent may block immuno-regulatory proteins on immune cells, such as cytotoxic T lymphocyte antigen-4 (CTLA-4), Programmed Death 1 (PD-1), PD-1 ligand 1 (PD-L1), OX40, KIR (Killer-cell Immunoglobulin-Like Receptor), or CD137. The immunotherapeutic agent may be, for example, an anti-CTLA-4 antibody, an anti-PD-1 antibody, an anti-PD-L1 antibody, an anti-KIR antibody, an OX40 agonist, a CD137 agonist, IL21 or other cytokines. In some embodiments, the immunotherapeutic agent may be an anti-CTLA-4 antibody, such as ipilimumab or tremelimumab.

The term “effective amount” refers to an amount of an immunotherapeutic agent described herein effective to “treat” a disease or disorder in a subject. In the case of cancer, the effective amount may cause any of the changes observable or measurable in a subject as described in the definition of “treating” and “treatment” above. For example, the effective amount can reduce the number of cancer or tumor cells; reduce the tumor size; inhibit or stop tumor cell infiltration into peripheral organs including, for example, the spread of tumor into soft tissue and bone; inhibit and stop tumor metastasis; inhibit and stop tumor growth; relieve to some extent one or more of the symptoms associated with the cancer, reduce morbidity and/or mortality; improve quality of life; increase or prolong overall survival; or a combination of such effects. In some embodiments, an effective amount may be an amount sufficient to decrease the symptoms of the cancer, or an amount sufficient to prolong overall survival. Efficacy in vivo can, for example, be measured by assessing the duration of survival (e.g. overall survival), time to disease progression (TTP), the response rates (RR), duration of response, and/or quality of life. Effective amounts may vary, as recognized by those skilled in the art, depending on route of administration, excipient usage, and co-usage with other agents.

The term “clinical response” refers to positive clinical outcome of a patient to the treatment defined above, and may be expressed in terms of various measures of clinical outcome. Positive clinical outcome may be considered as an improvement in any measure of patient status, including those measures ordinarily used in the art, such as tumor regression, a decrease in tumor (or lesion) size or growth, a decrease in tumor (or lesion) burden, an increase in the duration of Recurrence-Free interval (RFI), an increase in the time of Progression Free Survival (PFS), an increase in the time of Overall Survival (OS) (from treatment to death), an increase in the time of Disease-Free Survival (DFS), an increase in the duration of Distant Recurrence-Free Interval (DRFI), and/or an increase in the duration of response, and the like. Clinical response may be a complete or partial response, or stable or controlled disease progression. Clinical response may be measured, for example, at 2-4 weeks, 4-8 weeks, 8-12 weeks, 12-16 weeks, 4-6 months, 6-9 months, 9 months to 1 year, 1-2 years, 2-5 years, 5-10 years or longer, from initiation of treatment. For example, clinical response may be measured at week 8, 12, 16, 20, 24, or 36, survival at one year, 18 months, 2 years, 3 years, 4 years, 5 years, or 10 years, from initiation of treatment.

In some embodiments of the methods described herein, the likelihood of clinical response may be expressed in terms of the likelihood of an increase in the time of survival, such as longer overall survival, as compared to some patients, for example, a control or test patient group; patients who have a higher or lower expression level of a gene than the subject; patients who have a higher or lower score based on a formula and expression level of one or more genes; other patients treated with the immunotherapeutic agent; patients not treated with the immunotherapeutic agent; or patients treated with a different anti-cancer agent or procedure (e.g. surgical procedure). In some embodiments of the methods described herein, clinical response is expressed in terms of longer overall survival as compared to patients receiving the immunotherapeutic agent, e.g., ipilimumab or tremelimumab, who have a higher or lower expression level of a gene than the subject; or patients receiving the immunotherapeutic agent, e.g., ipilimumab or tremelimumab, who have a higher or lower score based on a formula and expression level of one or more genes. In some embodiments the term “longer overall survival” may mean overall survival longer than 6, 8, 9, 10, 12, or 18 months, or longer than 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 15, or 20 years. In some embodiments, “longer overall survival” may mean overall survival longer than 10, 20, 30, 40, 50, or 60 months.

In some embodiments, “likelihood of clinical response” may mean higher probability of survival at certain time points, for example, at 6, 8, 9, 10, 12, 18, 20, 30, 40, 50, or 60 months, or 1 year, 2 years, 3 years, 4 years, 5 years, 6 years, 10 years, or more than 10 years, from initiation of treatment, as compared to some patients, for example, a control or test patient group; patients who have a higher or lower expression level of a gene than the subject; patients who have a higher or lower score based on a formula and expression level of one or more genes; other patients treated with the immunotherapeutic agent; patients not treated with the immunotherapeutic agent; or patients treated with a different anti-cancer agent or procedure.

In some embodiments, the likelihood of clinical response may be expressed in terms of likelihood of an increase in the time of progression free survival (PSF). In some embodiments, “likelihood of clinical response” may mean the likelihood of an increase in the time of PSF as compared to some patients, for example, a control or test patient group; patients who have a higher or lower expression level of a gene than the subject; patients who have a higher or lower score based on a formula and expression level of one or more genes; a group of other patients treated with the immunotherapeutic agent; patients not treated with the immunotherapeutic agent; or patients treated with a different anti-cancer agent or procedure. In some embodiments, “likelihood of clinical response” may mean higher probability of PSF at certain time points, for example, at 1 year, 18 months, 2 years, 3 years, 5 years, 10 years, or more than 10 years, from initiation of treatment, as compared to some patients, for example, a control or test patient group; patients who have a higher or lower expression level of a gene than the subject; patients who have a higher or lower score based on a formula and expression level of one or more genes; other patients treated with the immunotherapeutic agent; patients not treated with the immunotherapeutic agent; or patients treated with a different anti-cancer agent.

The term “advanced cancer” means cancer that is no longer localized to the primary tumor site, or a cancer that is Stage III or IV according to the American Joint Committee on Cancer (AJCC). In some embodiments, the subject may have advanced cancer, such as advanced melanoma. Advanced melanoma may be, for example, metastatic melanoma, or stage III or IV melanoma, such as unresectable stage III or IV melanoma.

In some embodiments of the methods described herein, a blood sample may be obtained from the subject having cancer, and the expression level of at least one gene in the blood sample may be determined. The at least one gene may be selected from the genes listed in the first group of genes as listed in Table 2, wherein the expression level of the at least one gene is positively correlated with the likelihood of clinical response. For example, the at least one gene may be selected from IL2RB, KLRK1, G3BP, PPP1R16B, CLIC3, PRF1, SPON2, HOP, GNLY, TMEM161A, PRKCH, RUNX3, EOMES, SLC25A5, GZMB, IMP3, and ZAP70. It may be determined that the subject may have a high likelihood of clinical response, for example, longer overall survival, if the expression level of the at least one gene is higher than a predetermined value.

In some embodiments, the at least one gene may be selected from the genes listed in the second group of genes as listed in Table 3, wherein the expression level of the at least one gene is negatively correlated with the likelihood of clinical response. For example, the at least one gene may be selected from ASGR1, ASGR2, CENTA2, PGLS, MAPBPIP, STX10, C16ORF68, and RAB31. It may be determined that the subject may have a high likelihood of clinical response, for example, longer overall survival, if the expression level of the at least one gene is lower than a predetermined value.

In some embodiments, the expression level of at least two genes in the blood sample may be determined, and the likelihood of clinical response may be predicted based on the expression level of the at least two genes in the blood sample. The at least two genes may be selected from the genes listed in Tables 2 and 3. In some embodiments, the first gene of the at least two genes may be selected from the first group of genes as listed in Table 2, and a second gene of the at least two genes may be selected from the second group of genes as listed in Table 3. For example, the first gene may be selected from IL2RB, KLRK1, G3BP, PPP1R16B, CLIC3, PRF1, SPON2, HOP, GNLY, TMEM161A, PRKCH, RUNX3, EOMES, SLC25A5, GZMB, IMP3, and ZAP70. In some embodiments, the first gene may be IL2RB.

In some embodiments, the second gene of the at least two genes may be selected from ASGR1, ASGR2, CENTA2, PGLS, MAPBPIP, STX10, C16ORF68, and RAB31. For example, the second gene may be selected from ASGR1 and ASGR2.

In some embodiments, the at least two genes may be selected from the pairs of genes (two-gene signatures) listed in Tables 7 and 10 (see the Example section). In some embodiments, the first gene may be IL2RB and the second gene may be ASGR2. In some embodiments, the first gene may be IL2RB and the second gene may be ASGR1.

In some embodiments, the expression level of at least three genes in the blood sample may be determined, and the likelihood of clinical response may be predicted based on the expression level of the at least three genes in the blood sample. The at least three genes may be selected from the genes listed in Tables 2 and 3. A first gene of the at least three genes may be selected from the first group of genes as listed in Table 2. A second gene of the at least three genes may be selected from the second group of genes as listed in Table 3. In some embodiments, the at least three genes may be selected from three-gene groups (three-gene signatures) listed in Table 8 (see the Example section).

In some embodiments of the methods described herein, determining the likelihood of clinical response may comprise subjecting the expression level of the at least two genes to a formula to calculate a score, wherein the formula may be pre-determined by statistical analysis of (a) clinical response of a plurality of patients having the cancer to treatment with the immunotherapeutic agent and (b) the expression level of the at least two genes in pre-treatment blood samples from the plurality of patients. For example, coefficients may be calculated for each gene based on the clinical response and the gene expression level in the pre-treatment blood samples. The statistical analysis may be performed with any statistical method that is suitable for analyzing gene expression data, for example, Cox proportional-hazards (PH) regression.

In some embodiments, the formula for calculating the score is

Score=−C ₁ *X _(first gene) +C ₂ *X _(second gene),

wherein X_(first gene) and X_(second gene) may be expression level of the first and the second gene, respectively, and C1 and C2 may be, independently, pre-determined values. For example, C1 and C2 may be, independently, pre-determined coefficients of the first and the second gene, respectively, based on gene expression data obtained from pre-treatment blood samples from a patient group. For example, C1 and C2 may be each, independently, a number ranging from 0.01 to 3, wherein the score may be negatively correlated with the likelihood of survival.

In some embodiments, C₁ may range from 0.1 to 2.5, from 0.2 to 1.8, or from 0.3 to 1.4. In some embodiments, C₁ may be about 1.3.

In some embodiments, C₂ may range from 0.1 to 1.2, from 0.1 to 1.0, or from 0.2 to 0.8. In some embodiments, C₂ may be about 0.7 to 0.8.

In some embodiments, X_(first gene) and X_(second gene) may be mRNA expression level of the first and the second gene, respectively. For example, X_(first gene) and X_(second gene) may be mRNA expression level of IL2RB and ASGR2, respectively, or X_(first gene) and X_(second gene) may be mRNA expression level of IL2RB and ASGR1, respectively. The mRNA expression level may be normalized. In some embodiments, where the mRNA expression level is measured by microarray, the mRNA expression level may be normalized using a standard robust multichip average (RMA) approach.

In some embodiments, X_(first gene) and X_(second gene) may be mRNA expression level of IL2RB and ASGR2, respectively, C₁ may be about 1.3, and C₂ may be about 0.7 to 0.8.

The score described above may be compared to a predetermined threshold. A score that is lower than the threshold may be indicative of high likelihood of clinical response, for example, longer overall survival, or higher probability of survival at a time point, while a score that is higher than the threshold may be indicative of low likelihood of clinical response, for example, shorter overall survival, or lower probability of survival at a time point, as compared to a selected or control group of patients, such as, patients treated with the immunotherapeutic agent, patients not treated with the immunotherapeutic agent, or patients treated with a different anti-cancer agent or procedure.

The expression level of the at least one gene may be measured by at least one method selected from microarray, quantitative polymerase chain reaction (qPCR), and flow cytometry. “Microarray” refers to an ordered arrangement of hybridizable array elements, preferably polynucleotide probes, on a substrate.

The immunotherapeutic agent may be an antibody. In some embodiments, the immunotherapeutic agent may be an anti-CTLA4 antibody, such as a human or humanized or chimeric anti-CTLA4 antibody. In some embodiments, the immunotherapeutic agent may be ipilimumab or tremelimumab. In some embodiments, the immunotherapeutic agent may be ipilimumab

In some embodiments, the subject may have cancer selected from melanoma; prostate cancer, prostatic neoplasms, adenocarcinoma of the prostate; lung cancer, e.g., small cell lung cancer and non-small cell lung cancer; ovarian cancer; gastric cancer; adenocarcinoma of the gastric and gastro-esophageal junction; gastrointestinal stromal tumor; glioblastoma; cervical cancer; adenocarcinoma; breast cancer, invasive adenocarcinoma of the breast; pancreatic cancer; duct cell adenocarcinoma of the pancreas; sarcoma, such as chondrosarcoma, clear cell sarcoma of the kidney, endometrial stromal sarcoma, Ewing's sarcoma, osteosarcoma, peripheral primitive neuroectodermal tumor, ovarian sarcoma, soft tissue sarcoma, uterine sarcoma, adult soft tissue sarcoma, and synovial sarcoma; transitional cell carcinoma; urothelial carcinoma; Wilm's tumor and neuroblastoma; lymphoma; leukemia; ocular melanoma, intraocular melanoma, cutaneous melanoma; and kidney cancer. In some embodiments, the subject may have cancer selected from melanoma; prostate cancer, prostatic neoplasms, adenocarcinoma of the prostate; lung cancer, e.g., small cell lung cancer, non-small cell lung cancer; ovarian cancer; gastric cancer; and glioblastoma. In some embodiments, the subject may have advanced melanoma or metastatic melanoma. In some embodiments, the subject may have stage III or IV melanoma, such as unresectable stage III or IV melanoma. In some embodiments, the subject may have prostate cancer. In some embodiments, the subject may have lung cancer, e.g., small cell lung cancer or non-small cell lung cancer.

In some embodiments of the methods described herein, determining the likelihood of clinical response may be based on the gene expression level and at least one additional factor. In some embodiments, the at least one additional factor may be selected from baseline serum LDH level and disease stage (e.g., M category). In some embodiments, the at least one additional factor may be baseline serum LDH level.

In some embodiments, at the time the likelihood of clinical response of the subject is determined, the subject may be not being treated, or may have not been treated, with the immunotherapeutic agent. In some embodiments, the subject may have been treated with the immunotherapeutic agent at the time the likelihood of clinical response of the subject is determined. For example, the expression level of the at least one gene may change over time in the subject. Thus, the likelihood of clinical response may be determined to decide whether to administer (or re-administer) the immunotherapeutic agent to the subject.

Also provided are kits comprising one or more reagents for determining expression level of at least one gene in a blood sample, wherein the at least one gene is selected from a first group of genes as listed in Table 2 and a second group of genes as listed in Table 3. In some embodiments, the one or more reagents may be used to determine mRNA expression level of the at least one gene. For example, the kit may comprise at least one nucleic acid or polynucleotide capable of specifically hybridizing to the at least one gene. For example, the kit may comprise at least one probe set capable of specifically hybridizing to the at least one gene. In some embodiments, the kit may comprise at least one probe set for microarray. In some embodiments, the kit may comprise at least one reagent for performing quantitative polymerase chain reaction (qPCR). In some embodiments, the kit may comprise at least one reagent for flow cytometry.

In some embodiments, the kit may comprise one or more reagents for determining expression level of at least one gene selected from IL2RB, KLRK1, G3BP, PPP1R16B, CLIC3, PRF1, SPON2, HOP, GNLY, TMEM161A, PRKCH, RUNX3, EOMES, SLC25A5, GZMB, IMP3, and ZAP70. In some embodiments, the kit may comprise one or more reagents for determining expression level of at least one gene selected from ASGR1, ASGR2, CENTA2, PGLS, MAPBPIP, STX10, C16ORF68, and RAB31.

In some embodiments, the kit may comprise one or more reagents for determining expression level of at least two genes in the blood sample. The at least two genes may be selected from the genes listed in Tables 2 and 3. In some embodiments, the first gene of the at least two genes may be selected from the first group of genes as listed in Table 2. In some embodiments, a second gene of the at least two genes may be selected from the second group of genes as listed in Table 3. For example, the first gene may be selected from IL2RB, KLRK1, G3BP, PPP1R16B, CLIC3, PRF1, SPON2, HOP, GNLY, TMEM161A, PRKCH, RUNX3, EOMES, SLC25A5, GZMB, IMP3, and ZAP70. For example, the first gene may be IL2RB. In some embodiments, the second gene may be selected from ASGR1, ASGR2, CENTA2, PGLS, MAPBPIP, STX10, C16ORF68, and RAB31. For example, the second gene may be selected from ASGR1 and ASGR2. In some embodiments, the first gene may be IL2RB and the second gene may be ASGR2. In some embodiments, the first gene may be IL2RB and the second gene may be ASGR1. In some embodiments, the at least two genes may be selected from the pairs of genes listed in Tables 7 and 10 (Example section).

In some embodiments, the kit may comprise one or more reagents for determining expression level of at least three genes in the blood sample. The first gene of the at least three genes may be selected from the first group of genes as listed in Table 2. The second gene of the at least three genes may be selected from the second group of genes as listed in Table 3. In some embodiments, the at least three genes may be selected from three-gene groups listed in Table 8 (Example section).

The following Example contains additional information, exemplification and guidance which can be adapted to the practice of this invention in its various embodiments and the equivalents thereof. The example is intended to help illustrate the invention, and is not intended to, nor should it be construed to, limit its scope.

EXAMPLE Gene Signatures in Pre-Treatment Blood of Ipilimumab Treated Patients: Predictive and Prognostic Biomarkers of Response and Survival Introduction

Ipilimumab, a fully human monoclonal antibody against the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), promotes antitumor immunity and improves overall survival (OS) in metastatic melanoma patients.^(1,2)

Several markers have been found to associate with OS or tumor response in patients receiving ipilimumab, including tumor expression of immune-related genes,³ changes in absolute lymphocyte count (ALC),⁴ EOMES-positive CD8⁺ T cells,⁵ ICOS^(hi) CD4⁺ T cells,⁶ NY-ESO-1 seropositivity,⁷ polyfunctional NY-ESO-1 specific T cell responses,⁸ and baseline myeloid-derived suppressor cell (MDSC) levels.⁹

Despite these insights, no marker has yet emerged that meets five key criteria: (1) can be measured prior to treatment in a readily-accessible sample (e.g. blood), (2) is significantly associated with OS in patients receiving ipilimumab, (3) has a clear mechanistic explanation rooted in the underlying biology, (4) has been repeated in a test cohort independent from the training cohort on which it was developed, and (5) has an effect of a magnitude sufficient to provide clinically meaningful predictions of OS.

In this study biomarkers that meet those five criteria were identified by analyzing gene expression levels in blood drawn from 88 patients prior to receiving ipilimumab and then testing candidate predictive models in a separate cohort of 69 patients.

Materials and Methods

1. Study Design

The multicenter, phase II clinical trial CA184-004 enrolled 82 previously-treated and untreated patients with unresectable stage III or IV melanoma, randomized 1:1 into 2 arms to receive up to 4 intravenous infusions of either 3 or 10 mg/kg ipilimumab every 3 weeks (Q3W) in the induction phase. In the phase II CA184-007 trial, treatment-naïve or previously treated patients with unresectable stage III/IV melanoma (N=115) received open-label ipilimumab (10 mg/kg every 3 wks for four doses) and were randomized to receive concomitant blinded prophylactic oral budesonide (9 mg/d with gradual taper through week 16) or placebo. Data for baseline (pre-treatment) serum lactate dehydrogenase (LDH) were available for 154 out of 157 patients in the two studies (67 in CA184004 and 87 in CA184007). Clinical variables including OS and disease stage (M category) were recorded. Patient disease stage (M category) information for each cohort appears in Table 1. Complete study design, patient characteristics and endpoint reports of these trials have been described elsewhere^(10,11). Both studies were conducted in accordance with the ethical principles originating from the current Declaration of Helsinki and consistent with International Conference on Harmonization Good Clinical Practice and the ethical principles underlying European Union Directive 2001/20/EC and the United States Code of Federal Regulations, Title 21, Part 50 (21 C.F.R. 50). The protocols and patient informed consent forms received appropriate approval by all Institutional Review Boards or Independent Ethics Committees prior to study initiation. All participating patients (or their legally acceptable representatives) gave written informed consent for these biomarker focused studies.

TABLE 1 Disease stage (M Category) of patients in training and test cohorts Training Cohort (CA184-007) Test Cohort (CA184-004) M Category N (%) M Category N (%) M0 0 (0%) M0 1 (1.4%) M1A 17 (19%) M1A 17 (24.6%) M1B 29 (33%) M1B 5 (7.3%) M1C 42 (48%) M1C 46 (66.7%) Total 88 (100%) Total 69 (100%)

2. Affymetrix Gene Expression Analysis

Whole blood was collected prior to treatment. Total RNA was extracted using the Prism 6100 (Applied Biosystems, Foster City, Calif.), purified by RNAClean Kit (Agencourt Bioscience Corporation; Beverly, Mass.), and evaluated on a 2100 Bioanalyzer (Agilent Technologies, Santa Clara, Calif.). Complementary DNA preparation and hybridization on HT-HG-U133A 96-array plates followed manufacturer's protocols (Affymetrix, Santa Clara, Calif.).

3. Computational Analysis

The training cohort consisted of 88 patients from CA184007, and the test cohort comprised 69 patients from CA184004. All raw microarray data for the training and test cohorts were normalized together using a standard robust multichip average (RMA) approach,¹² which combines background adjustment, quantile normalization, and summarization, implemented in the Bioconductor package (v2.10, http://www.bioconductor.org)¹³ of the statistical computing language R (v2.15.1, http://www.r-project.org). For genes with multiple probes, the probe with the greatest mean expression level was selected.¹⁴

Feature Selection

A pathwise algorithm for Cox proportional-hazards (PH) regression, regularized by a lasso or elastic-net penalty, was applied to all probe sets for unique genes in the pre-treatment gene expression data from the training cohort to identify genes predictive of OS. This method has been previously described at length¹⁵ and is implemented as the glmnet package in the statistical computing language R. For much of the work the glmnet default alpha=1 (lasso penalty) was used, but it was also verified that alpha=0.95 yielded comparable results.

As a second method, a univariate Cox regression was applied to the pre-treatment gene expression data from the training cohort to rank the genes that were most significantly associated with OS.

Two-Gene Signature: Coefficient Estimation and Threshold Selection

Cox PH regression was used to estimate the coefficients for selected genes in order to best fit the OS data in the training cohort. Using the resulting coefficients and the gene expression values of the candidate genes, a two-gene score for each patient was calculated. For purposes of illustration, these scores were dichotomized by application of a classification threshold. This threshold was selected by minimizing, over all possible thresholds, the log-rank test p-value for comparing the OS curve in training-cohort patients with scores below the threshold to that in training-cohort patients with scores above the threshold.

Two-Gene Signature: Testing

For each patient in the test cohort, the coefficients previously estimated using the training cohort were used to calculate a score. Then the previously selected threshold was applied to classify patients into 2 groups, the Kaplan-Meier method¹⁶ was used to estimate the survival functions, and a log-rank test was used to compare OS in the 2 groups.

The scores for the training and test cohorts were then pooled, and the previously selected classification threshold was applied. Survival curves for the resulting 2 groups again were estimated by the Kaplan-Meier method and compared using a log-rank test.

Three-Factor Signature

Multivariable Cox PH regression was used to explore the relationship between selected genes and two of the most established prognostic factors in advanced melanoma: baseline serum lactate dehydrogenase (LDH) levels and disease stage (M category).¹⁷

An optimal three-factor signature (combining the previously-identified two-gene signature with LDH) was identified by performing a multivariable Cox regression on the training cohort to determine the best-fitting coefficients. Next, the comprehensive threshold exploration method described above was used to determine a good threshold.

Cell-Type Enrichment Analysis

A statistical method was developed to determine whether genes specific to particular cell types were over-represented in the set of genes positively associated with OS, and whether genes specific to particular cell types were over-represented in the set of genes negatively associated with OS. The publicly available Broad Institute Differentiation Map Portal (DMAP)¹⁸ data set was used. This data set contains a comprehensive collection of genome-wide gene expression profiles for all major human hematopoietic cell types in several replicates. To evaluate a given gene's cell-type specificity, for each gene profiled in the DMAP data an enrichment score was computed based on a published algorithm.¹⁹ Each enrichment score is a measure of how specific the expression of a particular gene is for a particular cell type. Next, for each cell type, cell-type specific gene sets were compiled using an enrichment score cut off of 10 as the criterion for inclusion of the gene into the gene set. Finally, separately for the set of genes positively associated with OS and the set of genes negatively associated with OS, a hypergeometric test was used to evaluate whether each gene set was enriched in genes specific for each of the cell types. The resulting hypergeometric p-values are reported in Tables 15-16, along with the hypergeometric p-values adjusted to control for false discovery rate (FDR) using the Benjamini-Hochberg method.

qPCR Data Analysis

Quantitative polymerase chain reaction (qPCR) was conducted using the TAQMAN® Gene Expression Assay (Life Technologies/Applied Biosystems) with Assay IDs Hs00172872_ml (EOMES) (target sequence RefSeq ID: NM_(—)005442.2) and Hs99999905_ml (GAPDH) (target sequence RefSeq ID: NM_(—)002046.4), respectively, according to methods previously described.³ The qPCR data were normalized using GAPDH as the housekeeping gene. An optimal threshold was identified using methods described above, and then a Kaplan-Meier plot was generated using R. The association with OS was determined by univariate Cox regression. In addition, Spearman's rank correlation was determined between the normalized EOMES expression by qPCR and the expression of selected genes by microarray.

Results Identification of Potential Predictive-Prognostic Gene Signatures in Ipilimumab Treated Patients

Two analytical methods were used to identify genes predictive of OS: elastic-net regularized Cox PH regression, and univariate (unregularized) Cox PH regression.

When the elastic-net regularized regression method was applied to the gene expression profiles for the selected probe sets for 13,341 unique genes from 88 patients in the training cohort (treated in the CA184007 trial), with the regularization parameter, lambda between 0.3713 and 0.2443, it identified a combination of two genes predictive of OS: IL2RB (interleukin-2 receptor beta, also known as CD122; probe 205291_at) and ASGR1 (asialoglycoprotein receptor 1; probe 206743_s_at). Relaxing lambda to a number between 0.2443 and 0.2226 to identify the next gene yielded ASGR2 (asialoglycoprotein receptor 2; probe 206130_s_at). Further, the gene expression profiles of ASGR1 and ASGR2 were found to be highly correlated in the training cohort (Spearman's rank correlation, R=0.562, P=1.22×10⁻¹⁴) (Table 4). The two genes also have a close biological relationship, encoding two proteins that together form the asialoglycoprotein receptor.²⁰

TABLE 4 Genes with expression most highly correlated with that of IL2RB and ASGR2 in both cohorts pooled, sorted by Spearman's rank correlation coefficient, R. IL2RB ASGR2 Gene Probe Set R P Value Gene Probe Set R P Value PRF1 214617_at 0.735 2.77E−28 CSPG2 221731_x_at 0.605 2.91E−17 RUNX3 204197_s_at 0.729 1.24E−27 FCN1 205237_at 0.588 3.71E−16 SPON2 218638_s_at 0.692 5.13E−24 CD14 201743_at 0.588 3.75E−16 CLIC3 219529_at 0.692 5.44E−24 GRN 200678_x_at 0.569 5.32E−15 RFTN1 212646_at 0.682 4.26E−23 ASGR1 206743_s_at 0.562 1.22E−14 CD247 210031_at 0.671 4.03E−22 APLP2 208248_x_at 0.551 5.26E−14 TXK 206828_at 0.665 1.11E−21 IFI30 201422_at 0.538 2.52E−13 PRKCH 218764_at 0.655 7.35E−21 TSPO 202096_s_at 0.537 2.96E−13 ZAP70 214032_at 0.644 5.51E−20 DUSP3 201536_at 0.532 5.55E−13 LUC7L2 220099_s_at 0.641 9.34E−20 HK3 205936_s_at 0.526 1.08E−12 FYN 210105_s_at 0.640 1.01E−19 CENTA2 219358_s_at 0.523 1.52E−12 SYNE1 209447_at 0.640 1.02E−19 STAB1 204150_at 0.520 2.26E−12 TH1L 220607_x_at 0.637 1.67E−19 LTA4H 208771_s_at 0.501 1.75E−11 CHST12 218927_s_at 0.636 2.05E−19 CYFIP1 208923_at 0.498 2.31E−11 GZMB 210164_at 0.634 2.72E−19 PLXNB2 208890_s_at 0.491 5.17E−11 DENND2D 221081_s_at 0.633 3.54E−19 GNA15 205349_at 0.489 5.94E−11 CBLB 209682_at 0.632 3.98E−19 CTSH 202295_s_at 0.488 6.61E−11 IARS 204744_s_at 0.628 8.65E−19 ANXA2P2 208816_x_at 0.488 6.84E−11 KLRD1 210606_x_at 0.627 9.92E−19 LILRB4 210152_at 0.471 3.82E−10 CCND2 200953_s_at 0.623 1.67E−18 CD33 206120_at 0.457 1.34E−09 PTGDR 215894_at 0.621 2.52E−18 ANXA2 210427_x_at 0.450 2.68E−09 GPR56 212070_at 0.620 2.90E−18 LGALS1 201105_at 0.399 1.90E−07 NONO 200057_s_at 0.616 5.12E−18 MAPRE2 202501_at 0.615 6.48E−18 HOP 211597_s_at 0.605 2.83E−17 STAT4 206118_at 0.605 2.88E−17 NCAM1 212843_at 0.604 3.56E−17 RNPS1 200060_s_at 0.603 4.00E−17 NKG7 213915_at 0.603 4.24E−17 EVL 217838_s_at 0.601 5.14E−17 KLRF1 220646_s_at 0.600 6.35E−17 PRKCQ 210038_at 0.598 8.34E−17 TGFBR3 204731_at 0.597 9.62E−17 PYHIN1 216748_at 0.597 9.66E−17 CCL4 204103_at 0.594 1.46E−16 RBBP7 201092_at 0.593 1.79E−16 KLRK1 205821_at 0.592 1.99E−16 PVRIG 219812_at 0.591 2.32E−16 SLC25A3 200030_s_at 0.591 2.55E−16 ST6GAL1 201998_at 0.590 2.70E−16 TBX21 220684_at 0.589 3.29E−16 GTF3C2 212429_s_at 0.586 4.87E−16 SIDT1 219734_at 0.586 5.14E−16 ARHGEF7 202548_s_at 0.584 6.53E−16 MAGED1 209014_at 0.584 6.54E−16 CD160 207840_at 0.582 8.66E−16 ADA 204639_at 0.581 9.91E−16 LPXN 216250_s_at 0.579 1.31E−15 CX3CR1 205898_at 0.579 1.34E−15 DNMT1 201697_s_at 0.576 1.85E−15 NFATC3 210555_s_at 0.576 2.06E−15 ATP2B4 212135_s_at 0.575 2.29E−15 PPP1R16B 212750_at 0.574 2.62E−15 TRA@//TRD@ 217143_s_at 0.574 2.63E−15 SMAD3 218284_at 0.573 2.91E−15 HSP90AB1 200064_at 0.572 3.55E−15 DDX47 220890_s_at 0.571 3.73E−15 CDC25B 201853_s_at 0.570 4.25E−15 PLEKHA1 219024_at 0.569 4.81E−15 CS 208660_at 0.568 6.10E−15 YPEL1 213996_at 0.566 7.16E−15 IL10RA 204912_at 0.566 7.54E−15 ITPR3 201189_s_at 0.566 7.73E−15 TMEM109 201361_at 0.566 7.86E−15 IMP3 221688_s_at 0.566 8.03E−15 NCALD 211685_s_at 0.565 8.51E−15 WWP1 212638_s_at 0.564 1.02E−14 SPTBN1 212071_s_at 0.562 1.30E−14 NPIP 204538_x_at 0.562 1.31E−14 KIFAP3 203333_at 0.562 1.32E−14 PLEKHF1 219566_at 0.561 1.38E−14 OFD1 203569_s_at 0.561 1.43E−14 CTSW 214450_at 0.561 1.47E−14 BLMH 202179_at 0.560 1.75E−14 AUTS2 212599_at 0.558 2.12E−14 GNLY 37145_at 0.557 2.54E−14 LCK 204891_s_at 0.556 2.65E−14 KIR3DL2 207314_x_at 0.555 3.32E−14 LOC339047 221501_x_at 0.554 3.39E−14 ZMYND11 202136_at 0.552 4.61E−14 SLC35E2 217122_s_at 0.549 6.37E−14 CRTC3 218648_at 0.548 7.38E−14

Applying the univariate (unregularized) Cox PH regression approach to the pre-treatment blood gene expression data from the 88 patients in the training cohort yielded 73 genes associated with OS with p<0.005 (Table 5), including a subset of 16 genes with p<0.001 (Table 6). IL2RB had the smallest p-value (p=4.62×10⁻⁷) in the training cohort, and higher expression of this gene was positively associated with longer survival (hazard ratio=0.28, 95% CI=0.17 to 0.46). Among the genes for which higher expression was associated with shorter survival (hazard ratio>1), ASGR1 and ASGR2 had the smallest p-values in the training cohort (P=1.18×10⁻⁶ and 1.42×10⁴, respectively).

TABLE 5 Top overall survival-associated genes in training cohort by univariate Cox PH regression analysis, p < 0.005. Hazard Ratio Gene Probe Set (95% CI) P Value IL2RB 205291_at 0.28 (0.17-0.46) 4.62E−07 ASGR1 206743_s_at 4.00 (2.30-6.94) 1.18E−06 KLRK1 205821_at 0.40 (0.26-0.62) 3.51E−05 G3BP 201503_at 0.17 (0.07-0.41) 6.44E−05 PPP1R16B 212750_at 0.20 (0.08-0.46) 1.24E−04 ASGR2 206130_s_at 2.05 (1.41-2.99) 1.42E−04 CLIC3 219529_at 0.45 (0.29-0.70) 1.58E−04 PRF1 214617_at 0.49 (0.34-0.70) 2.60E−04 SPON2 218638_s_at 0.53 (0.38-0.73) 3.77E−04 HOP 211597_s_at 0.50 (0.33-0.76) 4.76E−04 GNLY 37145_at 0.50 (0.34-0.73) 4.92E−04 TMEM161A 43977_at 0.12 (0.04-0.43) 6.26E−04 CENTA2 219358_s_at 3.99 (1.76-9.05) 6.43E−04 PRKCH 218764_at 0.50 (0.34-0.73) 6.75E−04 PGLS 218388_at  5.03 (1.89-13.37) 9.13E−04 RUNX3 204197_s_at 0.40 (0.24-0.69) 9.65E−04 CEBPA 204039_at 3.61 (1.65-7.88) 1.06E−03 GZMB 210164_at 0.50 (0.32-0.76) 1.07E−03 CCND2 200953_s_at 0.42 (0.25-0.70) 1.11E−03 ZBP1 208087_s_at 3.36 (1.67-6.76) 1.16E−03 NKG7 213915_at 0.48 (0.31-0.75) 1.17E−03 ARL2BP 202092_s_at 0.30 (0.15-0.62) 1.19E−03 CCL4 204103_at 0.53 (0.37-0.78) 1.31E−03 PMS2L11 210707_x_at 0.34 (0.18-0.65) 1.42E−03 ZMYND11 202136_at 0.49 (0.32-0.76) 1.72E−03 TTC17 218972_at 0.35 (0.19-0.67) 1.80E−03 MAPBPIP 218291_at  4.34 (1.73-10.91) 1.87E−03 CLDN15 219640_at 0.22 (0.08-0.58) 2.00E−03 TBX21 220684_at 0.49 (0.31-0.77) 2.09E−03 CEACAM3 208052_x_at 3.71 (1.57-8.75) 2.11E−03 ING2 205981_s_at 3.79 (1.67-8.60) 2.23E−03 LUC7L2 220099_s_at 0.40 (0.23-0.71) 2.28E−03 CAT 201432_at 0.40 (0.22-0.73) 2.30E−03 IMP3 221688_s_at 0.37 (0.20-0.70) 2.31E−03 CD2 205831_at 0.50 (0.33-0.76) 2.37E−03 GZMA 205488_at 0.55 (0.38-0.81) 2.39E−03 SPCS2 201240_s_at 0.37 (0.21-0.68) 2.47E−03 HOMER3 215489_x_at  4.22 (1.66-10.69) 2.57E−03 RPA2 201756_at 0.48 (0.31-0.76) 2.61E−03 RAB31 217763_s_at 3.31 (1.48-7.41) 2.63E−03 SLC25A5 200657_at 0.18 (0.07-0.52) 2.69E−03 ARF5 201526_at  4.80 (1.72-13.42) 2.70E−03 CHST12 218927_s_at 0.30 (0.13-0.68) 2.75E−03 MNAB 220202_s_at 0.31 (0.14-0.67) 3.01E−03 IL1RN 212657_s_at 2.36 (1.33-4.21) 3.02E−03 GPR56 212070_at 0.52 (0.34-0.80) 3.11E−03 TXNIP 201010_s_at 0.16 (0.05-0.54) 3.19E−03 CCND3 201700_at 0.34 (0.17-0.72) 3.38E−03 TRATRD 217147_s_at 0.56 (0.38-0.81) 3.45E−03 LILRA5 215838_at 1.87 (1.23-2.84) 3.47E−03 ZAP70 214032_at 0.48 (0.29-0.79) 3.48E−03 PYCARD 221666_s_at 3.67 (1.54-8.74) 3.49E−03 ADA 204639_at 0.37 (0.18-0.75) 3.69E−03 HPSE 219403_s_at 1.89 (1.23-2.92) 3.71E−03 TSPO 202096_s_at  3.96 (1.54-10.21) 3.71E−03 LOC130074 212017_at 0.33 (0.15-0.69) 3.82E−03 GFOD1 219821_s_at 0.41 (0.22-0.76) 4.13E−03 HLA-A /// 213932_x_at 0.18 (0.06-0.58) 4.15E−03 HLA-H /// LOC642047 /// LOC649853 /// LOC649864 CECR7 220452_x_at 0.16 (0.04-0.59) 4.23E−03 SERTAD3 219382_at  3.96 (1.51-10.38) 4.25E−03 C7ORF24 215380_s_at 0.24 (0.09-0.65) 4.31E−03 ZNF364 212742_at 0.20 (0.06-0.62) 4.34E−03 SULT1A1 215299_x_at 2.16 (1.26-3.71) 4.38E−03 S100A6 217728_at 3.69 (1.49-9.17) 4.41E−03 ID2 201565_s_at 0.33 (0.16-0.70) 4.42E−03 STX10 212625_at 3.51 (1.44-8.55) 4.47E−03 KLRD1 210606_x_at 0.55 (0.36-0.85) 4.57E−03 SH2D2A 207351_s_at 0.33 (0.15-0.73) 4.58E−03 MATK 206267_s_at 0.41 (0.23-0.75) 4.60E−03 IFI6 204415_at 1.49 (1.15-1.94) 4.88E−03 CDC25B 201853_s_at 0.54 (0.35-0.82) 4.92E−03 C16ORF68 218945_at 2.40 (1.33-4.35) 4.94E−03 GIMAP4 219243_at 0.25 (0.09-0.66) 4.97E−03

TABLE 6 Top overall survival-associated genes in training cohort by univariate Cox PH regression analysis, with p < 0.001 Hazard Ratio Gene Probe Set (95% CI) P Value IL2RB 205291_at 0.28 (0.17-0.46) 4.62E−07 ASGR1 206743_s_at 4.00 (2.30-6.94) 1.18E−06 KLRK1 205821_at 0.40 (0.26-0.62) 3.51E−05 G3BP 201503_at 0.17 (0.07-0.41) 6.44E−05 PPP1R16B 212750_at 0.20 (0.08-0.46) 1.24E−04 ASGR2 206130_s_at 2.05 (1.41-2.99) 1.42E−04 CLIC3 219529_at 0.45 (0.29-0.70) 1.58E−04 PRF1 214617_at 0.49 (0.34-0.70) 2.60E−04 SPON2 218638_s_at 0.53 (0.38-0.73) 3.77E−04 HOP 211597_s_at 0.50 (0.33-0.76) 4.76E−04 GNLY 37145_at 0.50 (0.34-0.73) 4.92E−04 TMEM161A 43977_at 0.12 (0.04-0.43) 6.26E−04 CENTA2 219358_s_at 3.99 (1.76-9.05) 6.43E−04 PRKCH 218764_at 0.50 (0.34-0.73) 6.75E−04 PGLS 218388_at  5.03 (1.89-13.37) 9.13E−04 RUNX3 204197_s_at 0.40 (0.24-0.69) 9.65E−04

Next, the 73 genes identified above were analyzed in all 2,628 possible two-gene and all 62,196 possible three-gene combinations. For each such combination, an unregularized Cox PH model to predict OS as an additive function of the two or three expression values was fit to the training-cohort data. A likelihood-ratio test was used to compare each model to a null (constant) model. Among the top 10 two-gene signatures in the training cohort (Table 7) by p-value (where p-value is used solely for ranking), two stood out as being the highest ranked: IL2RB+ASGR1 (p=1.56×10⁻¹⁰) and IL2RB+ASGR2 (p=2.79×10⁻¹⁰).

TABLE 7 Top two-gene signatures in training cohort by Cox PH regression analysis. Training Cohort Test Cohort Both Cohorts Gene 1 Gene 2 P Value P Value P Value IL2RB ASGR1 1.56E−10 2.21E−03 2.21E−13 IL2RB ASGR2 2.79E−10 5.00E−04 1.32E−13 IL2RB PGLS 1.25E−09 4.05E−02 3.00E−09 IL2RB CENTA2 2.31E−09 1.38E−02 1.47E−10 ASGR1 PRF1 3.23E−09 1.66E−02 3.15E−11 ASGR1 SLC25A5 3.80E−09 3.45E−03 6.23E−12 ASGR1 SPON2 6.36E−09 1.17E−02 3.95E−11 ASGR1 GNLY 9.32E−09 5.06E−02 3.78E−10 IL2RB MAPBPIP 1.06E−08 6.61E−03 3.07E−10 ASGR1 GZMB 1.11E−08 4.91E−02 2.02E−09

The three-gene signature with the smallest p-value in the training cohort was comprised of the combination of IL2RB, ASGR2, and CAT (catalase, probe 201432_at), p=2.41×10⁴¹. However, the p-value of this signature in the test cohort (as determined by applying the training model coefficients and threshold to the test cohort and calculating the log-rank p-value) was p=6.40×10⁻³, not below the p<0.001 threshold. To further explore the potential value of adding a third gene, possible three-gene signatures with a p<0.001 in the test cohort were examined. Among these, the three-gene signature with the smallest p-value in the training cohort (p=1.94×10⁻¹⁰) was IL2RB+ASGR2+ZBP1 (Z-DNA binding protein 1, probe 208087_s_at), with a significant p value also in the test cohort (p=9.53×10⁻⁴). For the training cohort, adding a third gene decreased the p-value for association with OS by at most one order of magnitude over the best two-gene signature (IL2RB+ASGR2). Furthermore, time-dependent Receiver Operating Characteristic (ROC) curves at 12 months²¹ show that the majority of the predictive power comes from IL2RB+ASGR2 (FIG. 4). In addition, among the top ten three-gene signatures in the training cohort (Table 8), six contained IL2RB and six contained either ASGR1 or ASGR2.

TABLE 8 Top three-gene signatures in training cohort by Cox PH regression analysis. Training Test Both Cohort Cohort Cohorts Gene 1 Gene 2 Gene 3 P Value P Value P Value IL2RB ASGR2 CAT 2.41E−11 6.40E−03 3.56E−13 IL2RB ASGR2 PGLS 3.13E−11 1.22E−02 2.28E−12 SPON2 PGLS SLC25A5 3.26E−11 1.64E−01 4.50E−08 IL2RB ASGR1 CAT 4.02E−11 1.57E−02 8.19E−13 IL2RB ASGR2 ASGR1 6.38E−11 2.99E−03 5.45E−14 SPON2 MAPBPIP SLC25A5 6.71E−11 1.48E−02 2.90E−11 IL2RB PGLS SLC25A5 6.97E−11 8.00E−02 2.60E−09 IL2RB ASGR1 SLC25A5 8.16E−11 3.57E−03 1.07E−13 PRF1 PGLS SLC25A5 8.42E−11 1.92E−01 1.07E−07 PRF1 ASGR1 SLC25A5 1.01E−10 5.45E−03 2.36E−13

In summary, two different methods converged on two signatures associated with OS in metastatic melanoma patients receiving ipilimumab: IL2RB+ASGR1 and IL2RB+ASGR2. Both signatures yielded comparable log-rank p-values and Kaplan-Meier plots in the training, test, and pooled cohorts (IL2RB+ASGR2, FIG. 1; IL2RB+ASGR1, FIG. 6). However, ASGR2 had a significantly higher mean expression level than ASGR1 (1.54-fold higher, P=1.32×10⁻⁶⁹ by paired t-test, FIG. 5), and therefore is likely to confer more consistency, less inter-assay variability and higher clinical robustness to a predictive signature. For this reason, the combination of IL2RB+ASGR2 was chosen as the primary two-gene signature for the analyses that follow.

The two coefficients for combining IL2RB and ASGR2 in a two-gene signature to predict OS were estimated using unregularized Cox PH regression in the training cohort. The estimated coefficients were −1.312 for IL2RB and 0.748 for ASGR2 (Table 9). The two-gene score for each patient could thus be calculated from the following equation: −1.312*X_(IL2RB)+0.748*X_(ASGR2), where X_(j) gives the log 2-scale RMA-normalized expression level for gene j. The signs of the coefficients indicate that higher expression of IL2RB was associated with longer survival (lesser hazard) whereas higher expression of ASGR2 was associated with shorter survival (greater hazard).

TABLE 9 Coefficients based on the training and test cohorts and the two cohorts pooled together, as well as coefficients based on regularized Cox regression. Training Cohort Test Cohort Both Cohorts Pooled Lambda Lambda Lambda Gene Model (by CV) Coefficient (by CV) Coefficient (by CV) Coefficient IL2RB alpha = 1 0.02895 −1.20684 0.115523 −0.36107 0.0417252 −0.804715 alpha = 0.95 0.023 −1.2291964 0.0696 −0.458378 0.0482 −0.791582 Unregularized 0 −1.3123 0 −0.5861 0 −0.9063 ASGR2 alpha = 1 0.02895 0.66974 0.115523 0.28155 0.0417252 0.5239357 alpha = 0.95 0.023 0.686752 0.0696 0.350097 0.0482 0.5149287 Unregularized 0 0.7475 0 0.4419 0 0.59948

In order to generate Kaplan-Meier plots evaluating the association of the two-gene score with OS, it was necessary to select a threshold separating scores for high risk patients (shorter survival) from those with low risk (longer survival). Thus, each possible threshold was applied to classify the training cohort into two risk groups, and a log-rank test was used to compare OS in the two groups (FIG. 7A). The threshold yielding the largest chi-square statistic was −5.80, with longer survivors having smaller score values and shorter survivors having greater values (FIG. 1A).

In order to test our findings from the training cohort, the same coefficients and threshold were applied to the gene expression data from patients in the test cohort (CA184004 trial). The two-gene signature maintained a highly significant association with OS in the test cohort (log-rank p=1.74×10⁻⁴) with a clear separation of the survival curve estimates (FIG. 1B).

Finally, for illustration purposes, training- and test-cohort scores were pooled for the same two-gene signature, using the coefficients and threshold estimated from the training-cohort data alone, and again estimated OS curves for the two resulting risk groups (FIG. 1C).

While the two-gene signatures comprised of IL2RB+ASGR2 and IL2RB+ASGR1 were optimal with regard to our model-selection criteria in the training cohort, and were significant and had good predictive accuracy in the test cohort, for completeness this study sought to identify additional pairs of genes that were strongly associated with OS in both the training and test cohorts. For the 2,628 possible two-gene signatures derived from the 73 best genes in the training cohort, Cox PH regression was used to estimate the coefficients and p-values in the training cohort, then the coefficients from the training cohort was applied to the test cohort and the resulting p-values determined. All signatures that had p<0.001 in both the training cohort and the test cohort were retained (Table 10). Then the same procedure was used in reverse: all genes with a univariate Cox regression p<0.005 in the test cohort were selected, then all two-gene combinations formed from those genes were evaluated and the ones with p<0.001 in both the test and training cohorts were retained. More than 88% of the resulting signatures included IL2RB or ASGR2 (Table 11).

TABLE 10 Two-gene signatures with p < 0.001 by Cox PH regression in both cohorts, sorted by training-cohort P value. Training Cohort Test Cohort Both Cohorts Gene 1 Gene 2 P Value P Value P Value IL2RB ASGR2 2.79E−10 5.00E−04 1.32E−13 IL2RB STX10 1.87E−07 7.97E−04 6.82E−10 IL2RB C16ORF68 4.55E−07 4.10E−04 4.59E−10 ASGR2 RUNX3 5.55E−07 3.99E−04 8.43E−10 ASGR2 IMP3 2.19E−06 8.47E−04 4.58E−09 ASGR2 SLC25A5 2.61E−06 4.72E−04 4.93E−10 ASGR2 C16ORF68 3.44E−05 3.05E−04 4.60E−09 ZAP70 STX10 2.30E−04 5.71E−04 5.39E−07 RAB31 C16ORF68 2.39E−04 5.14E−05 4.74E−07 STX10 C16ORF68 3.50E−04 2.11E−04 1.30E−06 RUNX3 STX10 3.88E−04 3.72E−04 1.58E−05 SLC25A5 STX10 5.25E−04 3.26E−04 2.74E−06 PRKCH C16ORF68 6.27E−04 3.80E−04 8.95E−06 RUNX3 C16ORF68 6.38E−04 9.48E−05 9.07E−06

TABLE 11 Additional two-gene signatures with p < 0.001 by Cox PH regression in both cohorts, determined by training on original test cohort and testing on original training cohort, and sorted by P Value in original training cohort. Original Original Test Training Both Cohort Cohort Cohorts Gene 1 Gene 2 P Value P Value P Value IL2RB ASGR2 4.81E−04 5.05E−10 1.66E−13 ASGR2 RUNX3 3.95E−04 5.29E−07 9.20E−10 IL2RB MT1M 3.04E−05 3.95E−06 2.37E−11 IL2RB C16ORF68 3.51E−05 4.66E−06 1.19E−09 ASGR2 WBP11 2.03E−04 5.98E−06 5.01E−09 ASGR2 EIF4B 8.09E−04 6.39E−06 2.25E−09 IL2RB HIST2H2AA /// 3.52E−04 6.82E−06 2.16E−09 LOC653610 /// H2AR ASGR2 RFTN1 9.59E−05 1.08E−05 4.71E−08 IL2RB IFI27 2.41E−06 1.09E−05 1.24E−10 IL2RB AMFR 4.60E−04 1.13E−05 9.65E−10 IL2RB FOLR3 1.80E−05 1.42E−05 5.33E−10 ASGR2 AMFR 1.51E−04 1.83E−05 3.04E−10 IL2RB C4A /// C4B 1.94E−04 1.88E−05 3.51E−08 IL2RB VPREB3 3.07E−04 1.89E−05 3.98E−08 ASGR2 C4A /// C4B 1.67E−05 2.16E−05 6.90E−10 RBBP7 ASGR2 3.96E−04 2.36E−05 1.54E−08 IL2RB FTHP1 6.47E−04 2.74E−05 1.24E−06 IL2RB HK3 5.36E−04 2.99E−05 7.44E−08 ASGR2 ZAP70 9.49E−04 3.16E−05 1.02E−08 IL2RB KIAA1026 2.66E−04 3.26E−05 3.08E−08 IL2RB ACTA2 3.13E−05 3.82E−05 7.67E−10 IL2RB FTH1 8.81E−05 4.41E−05 8.58E−06 IL2RB SLC7A1 1.85E−07 5.45E−05 1.43E−10 ASGR2 C16ORF68 1.78E−04 5.46E−05 9.66E−09 ASGR2 HSPA8 4.44E−04 7.11E−05 1.68E−08 IL2RB SUMO2 6.35E−04 7.21E−05 2.41E−07 ASGR2 HNRPH1 5.96E−04 7.25E−05 2.15E−08 IL2RB HP /// HPR 8.00E−05 7.64E−05 8.25E−09 IL2RB GTF3A 4.37E−04 7.71E−05 8.72E−07 IL2RB LOC171220 3.96E−05 8.25E−05 3.81E−05 FOXO3A IL2RB 5.36E−04 8.34E−05 2.48E−06 IL2RB TCF3 6.30E−06 8.75E−05 7.56E−08 ASGR2 CD247 7.57E−04 9.46E−05 6.59E−08 ASGR2 MAGED1 5.19E−04 1.01E−04 6.89E−07 ASGR2 CAMP 2.97E−06 1.06E−04 1.40E−09 ASGR2 XBP1 5.16E−04 1.12E−04 2.61E−08 ASGR2 IFI27 1.70E−05 1.14E−04 9.88E−10 IL2RB CA4 3.67E−04 1.30E−04 2.12E−07 ASGR2 LOC171220 2.29E−04 1.44E−04 4.79E−05 IL2RB NCF1 /// 2.28E−04 1.57E−04 1.51E−08 LOC653361 /// LOC653840 ASGR2 MTMR1 2.37E−05 1.63E−04 1.57E−08 IL2RB HSPA6 /// 4.48E−04 1.66E−04 5.98E−07 LOC652878 C4A /// C4B RAB31 6.00E−05 1.66E−04 5.94E−07 IL2RB ACTN1 7.68E−04 1.66E−04 1.98E−07 ASGR2 IL10RA 2.36E−04 1.69E−04 3.04E−07 ASGR2 SUMO2 2.71E−04 1.82E−04 5.19E−08 ASGR2 HP /// HPR 4.21E−04 1.91E−04 1.65E−08 IL2RB PQLC1 1.79E−04 1.92E−04 1.52E−07 ASGR2 TCF3 1.19E−05 1.95E−04 3.51E−08 IL2RB HNRPH1 4.93E−04 1.95E−04 2.83E−07 IL2RB MAG 2.75E−05 1.98E−04 1.39E−08 IL2RB WNK1 9.21E−05 2.01E−04 5.41E−07 IL2RB HIST1H2BD 2.83E−04 2.14E−04 4.80E−08 ASGR2 EVL 4.26E−04 2.30E−04 1.15E−07 RAB31 C16ORF68 3.82E−05 2.37E−04 3.45E−07 ASGR2 FTH1 4.46E−04 2.46E−04 1.33E−05 ASGR2 FAM102A 3.02E−04 2.50E−04 1.41E−07 ASGR2 NPM1 5.13E−04 2.57E−04 1.80E−07 IL2RB HSPA6 2.72E−04 2.59E−04 3.81E−07 ASGR2 FOLR3 3.22E−06 2.68E−04 7.96E−10 IL2RB FAM102A 1.95E−04 2.86E−04 4.65E−07 IL2RB HLADQB1 /// 1.25E−05 3.10E−04 1.28E−08 LOC650557 IL2RB RALBP1 2.13E−04 3.22E−04 7.06E−08 IL2RB ECGF1 4.85E−04 3.26E−04 1.54E−06 ASGR2 MAP3K4 5.38E−04 3.46E−04 2.54E−06 IL2RB PPP1R10 4.73E−06 3.61E−04 1.03E−09 ASGR2 PDCD4 4.33E−04 3.64E−04 1.24E−06 RUNX3 KIAA0690 7.23E−04 3.75E−04 1.10E−06 IL2RB MTMR1 3.55E−04 3.94E−04 1.13E−06 IL2RB CKAP4 3.83E−05 4.14E−04 8.02E−08 RFTN1 RAB31 5.89E−04 4.17E−04 6.86E−05 ASGR2 KIAA1026 1.24E−04 4.18E−04 4.68E−08 IL2RB P2RX5 9.59E−05 4.21E−04 3.48E−07 IL2RB ZAP70 7.15E−04 4.27E−04 7.38E−07 IFI27 RAB31 7.89E−06 4.32E−04 6.29E−08 ASGR2 KIAA0746 5.33E−04 4.36E−04 1.83E−07 IL2RB UBE2M 9.69E−06 4.55E−04 6.23E−06 IL2RB PGCP 2.49E−04 4.70E−04 4.14E−07 IL2RB NAGK 2.73E−04 4.91E−04 6.93E−07 IL2RB MARK3 1.56E−04 4.92E−04 1.17E−05 IL2RB ENDOD1 9.02E−06 4.97E−04 1.08E−07 IL2RB CD6 1.51E−04 5.14E−04 5.39E−07 IL2RB MRPL46 2.26E−04 5.34E−04 1.51E−04 C4A /// C4B KIAA0690 3.40E−05 5.50E−04 7.24E−08 IL2RB HDAC5 1.25E−05 5.66E−04 1.27E−07 ASGR2 NOL7 8.39E−04 5.81E−04 4.07E−06 ASGR2 LCN2 1.12E−09 5.84E−04 6.77E−11 RUNX3 MT1M 1.24E−04 6.51E−04 7.87E−08 IL2RB HPCAL1 1.70E−04 6.53E−04 1.87E−06 MTF1 C4A /// C4B 9.36E−05 6.55E−04 3.71E−08 IL2RB SMO 3.17E−04 6.73E−04 9.23E−07 ASGR2 MARK3 9.66E−05 6.87E−04 1.19E−06 ASGR2 RALBP1 4.75E−05 6.88E−04 4.14E−08 IL2RB TALDO1 5.83E−04 6.91E−04 6.20E−06 AMFR RAB31 3.22E−04 6.97E−04 7.85E−08 ASGR2 CIRBP 6.12E−04 7.00E−04 4.53E−07 IL2RB HLADQA1 1.08E−05 7.16E−04 1.02E−08 IL2RB UBE2G2 7.87E−04 7.19E−04 3.22E−06 ASGR2 GOLGA8G /// 2.18E−04 7.21E−04 1.08E−07 GOLGA8D /// LOC388189 /// GOLGA8E /// GOLGA8C /// GOLGA8F IL2RB HIP1R 2.50E−04 7.41E−04 6.31E−06 ASGR2 TCN1 1.09E−05 7.52E−04 1.17E−08 IL2RB C2ORF17 2.00E−05 7.56E−04 1.59E−08 IL2RB DHX34 5.38E−05 7.76E−04 7.76E−07 RUNX3 C16ORF68 3.81E−05 8.04E−04 4.76E−06 ZAP70 KIAA0690 3.81E−04 8.28E−04 2.65E−07 HNRPH1 DHX34 1.19E−04 8.47E−04 7.65E−07 ASGR2 PQLC1 6.91E−05 8.62E−04 8.70E−08 IL2RB BLR1 4.49E−06 8.90E−04 1.13E−07 IL2RB TSTA3 3.80E−04 8.99E−04 4.62E−06 IL2RB VTI1B 5.48E−05 9.10E−04 1.46E−06 TCF3 RAB31 5.63E−07 9.45E−04 2.27E−06 MTF1 RFTN1 3.28E−04 9.49E−04 2.84E−06 ZAP70 HIST2H2AA /// 2.90E−04 9.59E−04 2.96E−07 LOC653610 /// H2AR ASGR2 GTF3A 1.32E−04 9.76E−04 9.90E−07

The Three-Factor Signature and Overall Survival

To determine whether the two-gene signature, IL2RB+ASGR2, was an independent predictor of OS given established prognostic factors in metastatic melanoma, we performed a multivariable Cox PH regression analysis including the expression levels of each of the genes or that of the two-gene signature as well as baseline serum LDH levels or disease stage (M category). The results suggest that the two-gene signature was an independent predictor of OS in this context in the training, test, and pooled cohorts (Table 12). Each p-value is for a likelihood-ratio test comparing the full model to a model that excludes the corresponding variable. Similarly, expression of each of the individual genes that comprise the two-gene signature (Table 13) also was an independent predictor of OS given baseline serum LDH levels or disease stage (M Category) in the training, test, and pooled cohorts. The two-gene signature was also an independent predictor of OS when absolute lymphocyte count (ALC) at baseline or prior to the third ipilimumab dose was added to the multivariable Cox PH model (Table 14).

TABLE 12 Marginal tests of significance from multivariable Cox PH regression Coefficient Variable Estimate P Value Training Cohort LDH 0.0012  0.042 2-Gene Signature 0.82 1.3 × 10⁻⁶ M1B vs M1A −0.72 0.14 M1C vs M1A 0.26 0.55 Test Cohort LDH 0.0025 1.9 × 10⁻⁴ 2-Gene Signature 0.54 5.5 × 10⁻⁴ M1B vs M1A 0.70 0.31 M1C vs M1A 0.95  0.011 Both Cohorts Pooled LDH 0.0017 4.6 × 10⁻⁵ 2-Gene Signature 0.62 7.6 × 10⁻⁹ M1B vs M1A −0.23 0.55 M1C vs M1A 0.69  0.013

TABLE 13 Multivariable Cox PH regression showing that each key gene individually was an independent predictor of OS, given both baseline LDH and M Category. IL2RB ASGR2 ASGR1 Coefficient Coefficient Coefficient Variable Estimate P Value Variable Estimate P Value Variable Estimate P Value Training Cohort Training Cohort Training Cohort LDH 0.0019 8.8 × 10⁻⁴ LDH 0.0018 2.6 × 10⁻³ LDH 0.0016 1.2 × 10⁻² IL2RB −1.04   9 × 10⁻⁵ ASGR2 0.45 1.7 × 10⁻² ASGR1 0.81 1.1 × 10⁻² M1B vs M1A −0.64 0.19 M1B vs M1A −0.49 0.32 M1B vs M1A −0.47 0.33 M1C vs M1A 0.30 0.49 M1C vs M1A 0.49 0.25 M1C vs M1A 0.34 0.44 Test Cohort Test Cohort Test Cohort LDH 0.0026 6.4 × 10⁻⁵ LDH 0.0025 1.2 × 10⁻⁴ LDH 0.0026 8.5 × 10⁻⁵ IL2RB −0.66 1.6 × 10⁻² ASGR2 0.72 6.8 × 10⁻⁴ ASGR1 0.61 5.2 × 10⁻² M1B vs M1A 0.48 0.48 M1B vs M1A 0.42 0.53 M1B vs M1A 0.33 0.62 M1C vs M1A 0.76 3.7 × 10⁻² M1C vs M1A 0.98 7.9 × 10⁻³ M1C vs M1A 0.86 1.8 × 10⁻² Both Cohorts Both Cohorts Both Cohorts Pooled Pooled Pooled LDH 0.0022 1.6 × 10⁻⁷ LDH 0.0019 3.5 × 10⁻⁶ LDH 0.00020 1.8 × 10⁻⁶ IL2RB −0.81 1.2 × 10⁻⁵ ASGR2 0.55 5.7 × 10⁻⁵ ASGR1 0.68  1.0 × 1.0⁻³ M1B vs M1A −0.36 0.33 M1B vs M1A −0.26 0.50 M1B vs M1A −0.16 0.68 M1C vs M1A 0.55 4.2 × 10⁻² M1C vs M1A 0.71 9.8 × 10⁻³ M1C vs M1A 0.62 2.2 × 10⁻²

TABLE 14 Multivariable Cox PH regression showing that the two-gene signature was an independent predictor of OS, given ALC (at baseline or prior to dose 3), LDH, and M category. Coefficient Variable Estimate P Value Baseline ALC (ALC1) Training Cohort 2-Gene Signature 0.846 3.2 × 10⁻⁶ LDH 0.0011 0.08 ALC1 0.110 0.67 M1B vs M1A −0.701 0.16 M1C vs M1A 0.249 0.57 Test Cohort 2-Gene Signature 0.522 0.0092 LDH 0.00288 0.033 ALC1 0.209 0.34 M1B vs M1A 0.38 0.64 M1C vs M1A 1.06 0.019 Both Cohorts Pooled 2-Gene Signature 0.65 1.4 × 10⁻⁷ LDH 0.00164 2.2 × 10⁻³ ALC1 0.154 0.32 M1B vs M1A −0.152 0.71 M1C vs M1A 0.799 9.0 × 10⁻³ ALC Prior to Dose 3 (ALC3) Training Cohort 2-Gene Signature 0.792 1.1 × 10⁻⁵ LDH 0.00112 0.075 ALC3 −0.127 0.56 M1B vs M1A −0.756 0.13 M1C vs M1A 0.204 0.64 Test Cohort 2-Gene Signature 0.403 0.023 LDH 0.00249 0.069 ALC3 −0.385 0.065 M1B vs M1A 0.488 0.550 M1C vs M1A 0.852 0.046 Both Cohorts Pooled 2-Gene Signature 0.572 9.9 × 10⁻⁷ LDH 0.00155 4.4 × 10⁻³ ALC3 −0.267 0.071 M1B vs M1A −0.338 0.39 M1C vs M1A 0.662 0.027

As it was established that LDH and the two-gene signature, IL2RB+ASGR2, were independent predictors of OS, it was next determined whether the two-gene signature could be improved by combining it with LDH to create a three-factor signature. Coefficients were estimated using Cox PH regression on the training cohort (0.00158 for LDH and 0.816 for the two-gene signature). The three-factor score for each patient could thus be calculated from the following equation: 0.00158*Y_(LDH)+0.816*(−1.312*X_(IL2RB)+0.748*X_(ASGR2)), where Y_(j) gives the concentration of factor j. Next the log-rank p-value was calculated for all possible thresholds. The threshold with the smallest p-value was −4.437 (FIG. 7B). The Kaplan-Meier curves were plotted for the training cohort (FIG. 2A), then the same coefficients and threshold were applied to the test cohort (FIG. 2B), yielding a log-rank p-value of p=1.74×10⁻⁵. The Kaplan-Meier plot for both cohorts pooled together appears in FIG. 2C.

It was next determined whether using two thresholds instead of one could provide better separation among survival curves. Using the three-factor signature described above with coefficients from the training cohort, two-threshold exploration was performed on the pooled cohort. Using thresholds at both −5.29 and −3.62 (FIG. 7C), three groups of patients were identified that corresponded to high, intermediate and low risk (FIG. 2D).

Time dependent ROC curves at 12 months were then plotted for both the two-gene signature (IL2RB+ASGR2) and the three-factor signature (IL2RB+ASGR2+LDH) in the training cohort (FIG. 2E), test cohort (FIG. 2F), and both cohorts pooled (FIG. 2G). These curves show that at best, baseline LDH only slightly improves predictive performance when added to the two-gene signature.

Functional and Gene Set Enrichment Analysis

This study also sought to determine whether the various gene sets emerging in the above analyses were characteristic of particular blood cell types. Among the genes most highly correlated with IL2RB across the pooled training and test cohorts, the top two were PRF1 (perforin 1, probe 214617_at) (Spearman R=0.735, p=2.77×10⁻²⁸) and RUNX3 (runt-related transcription factor 3, probe 204197_s_at) (Spearman R=0.729, p=1.24×10⁻²⁷) (Table 5), genes that are highly interrelated, established to be associated with T-cells,^(22,23) and point clearly to underlying biological mechanisms (see Discussion). Also present among the 100 genes most correlated with IL2RB are a number of other genes established to be associated with T-cells including CD247,²⁴ LCK,²⁵ FYN,²⁵ ZAP70,²⁶ CBLB,²⁷ and TXK.²⁸ RUNX3, PRF1, and ZAP70 are also present on the list of genes associated with OS by univariate Cox regression with p<0.005. RUNX3 has been reported to induce transcription of PRF1 and EOMES (eomesodermin),²² which has been implicated in the regulation of IL2RB expression.²⁹ These analyses pointed to a role for EOMES as a central regulator of the expression of various genes in our model (FIG. 3A). Since there were no probes on the HT-HG-U133A 96-array for testing the expression of this gene, the expression of EOMES was tested separately by qPCR. There was significant association between the expression of EOMES and overall survival by both log-rank test (p=6.86×10⁻⁸) (FIG. 8) and univariate Cox regression (p=1.808×10⁻³). In addition, expression of key genes as determined by microarray were all highly correlated with EOMES expression (by qPCR) as determined by Spearman's rank correlation, including IL2RB (R=0.474, p=1.50×10⁻⁵), PRF1 (R=0.585, p=2.90×10⁻⁸), and RUNX3 (R=0.594, p=1.57×10⁻⁸).

Among the genes most highly correlated with ASGR2 are ASGR1, CD14 (cluster of differentiation 14, probe 201743_at) (Spearman R=0.588, p=3.75×10⁻¹⁶), and CD33 (cluster of differentiation 33, probe 206120_at) (Spearman R=0.457, p=1.34×10⁻⁹) (Table 5). CD14 expression is a characteristic of myeloid-derived suppressor cells (MDSCs) in melanoma patients,⁹ and CD33 expression is a characteristic of myeloid cells more generally.³⁰ Our cell type enrichment analysis found that among the 73 genes associated with OS by univariate Cox PH regression (p<0.005), the set of genes negatively associated with OS was most enriched in genes specific for CD14+ monocytes (P=2.17×10⁻⁷) (P values by hyper-geometric test as described in Methods), and also highly enriched in genes specific for CD33+ monocytes (P=2.62×10⁻⁴) as well as two types of granulocytes (Table 15). This is illustrated graphically (FIG. 3B, lower right) in a heat map of the DMAP¹⁸ expression data by cell type (columns) for the set of genes negatively associated with OS (rows).

TABLE 15 Enrichment of genes specific for particular cell types in the list of genes negatively associated with OS, including adjusted hypergeometric P values. Cell Type Score P-value Adjusted P-value MONO2|CD14+|CD45dim 36.64 1.11E−08 2.17E−07 GRAN2|CD34−|SSChi|CD45+|CD11b+|CD16− 25.54 4.64E−07 6.04E−06 MONO1|CD34−|CD33+|CD13+ 13.91 2.69E−05 2.62E−04 GRAN3|CD16+|CD11b+ 10.18 3.74E−03 2.91E−02

The set of genes positively associated with OS was most enriched in genes specific for two types of NK cells (CD56⁺CD16⁺CD3⁻, P=2.50×10⁻¹⁸ and CD56⁻CD16⁻CD3⁻, P=7.95×10⁻¹²) and two types of T cells (CD8⁺CD62L⁻CD45RA⁺, P=3.41×10⁻¹⁷ and CD8⁺CD62L⁻CD45RA⁻, P=8.05×10⁻¹⁴) (Table 16) (P values by hyper-geometric test as described in Methods). This is illustrated graphically (FIG. 3B, top and middle) in a heat map of the DMAP expression data¹⁸ by cell type (columns) for the set of genes positively associated with OS (rows).

TABLE 16 Enrichment of genes specific for particular cell types in the list of genes positively associated with OS, including adjusted hypergeometric P values. Cell Type Score P-value Adjusted P-value NKA2|CD56+|CD16+|CD3− 53.89 1.28E−19 2.50E−18 TCELLA1|CD8+|CD62L−|CD45RA+ 42.86 2.62E−18 3.41E−17 TCELLA3|CD8+|CD62L−|CD45RA− 34.51 8.26E−15 8.05E−14 NKA3|CD56−|CD16−|CD3− 41.42 1.02E−12 7.95E−12 GRAN3|CD16+|CD11b+ 32.67 3.37E−09 2.19E−08 TCELLA4|CD8+|CD62L+|CD45RA− 15.54 8.98E−09 5.00E−08 NKA4|CD14−|CD19−|CD3+|CD1d+ 2.95 7.20E−06 3.51E−05 MEGA2|CD34−|CD41+|CD61+|CD45− 2.86 8.97E−04 3.89E−03 GRAN1|CD34−|SSChi|CD45+|CD11b−|CD16− 9.78 1.65E−03 6.44E−03 TCELLA2|CD8+|CD62L+|CD45RA+ 9.80 1.98E−03 7.01E−03 TCELLA7|CD4+|CD62L−|CD45RA− 5.12 2.38E−03 7.73E−03

Taken together, these analyses suggest that greater expression of genes more highly expressed in natural killer (NK) and T-cells (such as IL2RB) was associated with longer survival, while greater expression of genes expressed in CD14⁺ cells and other myeloid lineage cells (such as ASGR1 and ASGR2) was associated with shorter survival (FIG. 3C).

Discussion

Ongoing research aims to discover biomarkers that could select patients with an enhanced benefit/risk profile. Whereas ipilimumab has shown significant survival benefit in a subset of metastatic melanoma patients, in some patients the treatment can result in adverse events. Thus, identification of biomarkers that can predict a patient's response and are easily measured in peripheral blood is important. In the present study, a novel approach was used to identify blood gene-signatures that may predict OS in metastatic melanoma patients receiving ipilimumab.

When using microarray data to develop predictive gene-signatures there is a high likelihood of developing a signature that may be strongly associated with OS in a training cohort, but not significantly associated with OS in a test cohort, due to over-fitting in the training cohort. Signatures consisting of large numbers of genes are more likely to suffer from over-fitting and are less practical in the clinical context.

Using gene expression microarray data from a training cohort of 88 patients, two independent methods were applied to evaluate association of gene expression with OS. Results from both methods pointed to a lead two-gene signature of IL2RB+ASGR2 that was highly associated with OS in the training cohort. Using these two genes, a signature was calculated that included two coefficients and a threshold in the training cohort, and it was determined that the same signature was also significantly associated with OS in an independent test cohort of 69 patients (p<0.001). The signature also had strong predictive performance in the independent test cohort (AUC=0.818 for a time-dependent ROC curve at 12 months).

The size of the signature is noteworthy. While signatures comprised of many genes carry risk of over-fitting, a two-gene signature significantly mitigates this risk. Adding additional genes improved the signature incrementally, but in this study, the majority of the predictive power came from the combination of two top genes, IL2RB and ASGR2.

Mechanistic investigation of the two genes with expression most highly correlated with that of IL2RB (RUNX3 and PRF1) yielded insights into its underlying biology. RUNX3 has been reported to induce transcription of PRF1 and EOMES (eomesodermin),²² which has been implicated in the regulation of IL2RB expression.²⁹ Based on the high correlation between IL2RB, RUNX3, and PRF1 expression and the mechanistic linkage between EOMES, RUNX3 and IL2RB, it may be hypothesized that EOMES is a core transcription factor that underlies the observed coexpression of IL2RB, RUNX3 and PRF1 in the data. Further analyses of EOMES by qPCR supported this notion, as we found strong correlation of the expression levels of EOMES and other genes in our model. Greater baseline expression levels of this gene were also associated with longer survival in the data set. Moreover, a direct relationship between EOMES and CTLA-4 has been established,³¹ as well as interactions between EOMES and IFNγ,²² the factor underlying many of the tumor chemokine changes linked with ipilimumab response (FIG. 3A).³

Mechanistic investigation of ASGR2 linked it to myeloid cells and particularly MDSCs, as its expression was highly correlated with the MDSC surface markers CD14 and CD33.^(9,30) MDSCs have the capacity to suppress both the cytotoxic activities of natural killer (NK) and natural killer T (NKT) cells, and the adaptive immune response mediated by CD4⁺ and CD8⁺ T cells. MDSCs act through multiple pathways including upregulation of nitric oxide synthase 2 (NOS2) and production of arginase 1 (ARG1). ARG1 and NOS2 metabolize L-arginine and either together, or separately, block translation of the T cell CD3 zeta chain, inhibit T cell proliferation, and promote T cell apoptosis.³² Additionally, MDSCs are believed to secrete immunosuppressive cytokines such as TGFβ and induce regulatory T cell development.³⁰ High frequency of MDSCs have been reported in the peripheral blood of patients affected by breast, lung, renal and head and neck carcinomas³³ and in melanoma.³⁴

While in this study gene expression was mainly measured via microarray, it may also be assayed via quantitative polymerase chain reaction (qPCR). Moreover, IL2RB and ASGR2 are both cell surface markers and therefore may be detected via flow cytometry. The magnitude of the two-gene signature may change over time in a given patient (either inherently or in response to additional therapies such as a CD137-agonist), and may be monitored to determine the best times to administer or re-administer ipilimumab.

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TABLE 17 Probe Sets Target Name Probe Set ID SEQ ID NO. Probe Sequences Target Sequence Target Genbank ID SLC25A3 200030_s_at 1 TCATCATGATTGGTACCCTGACTGC acaccatgatgaagttcgcctgctttgaacgtactgttgaagcactgtacaag NM_002635.1 tttgtggttcctaagccccgcagtgaatgttcaaagccagagcagctggttgt aacatttgtagcaggttacatagctggagtcttttgtgcaattgtttctcacc ctgctgattctgtggtatctgtgttgaataaagaaaaaggtagcagtgcttct ctggtcctcaagagacttggatttaaaggtgtatggaagggactgtttgcccg tatcatcatgattggtaccctgactgcactacagtggtttatctatgactccgtgaag gtctacttcagacttcctc 2 GTACCCTGACTGCACTACAGTGGTT 3 GTGGTTTATCTATGACTCCGTGAAG 4 GTGAAGGTCTACTTCAGACTTCCTC 5 ACACCATGATGAAGTTCGCCTGCTT 6 TCGCCTGCTTTGAACGTACTGTTGA 7 TGTACAAGTTTGTGGTTCCTAAGCC 8 TCCTAAGCCCCGCAGTGAATGTTCA 9 ACCCTGCTGATTCTGTGGTATCTGT 10 AAAGGTAGCAGTGCTTCTCTGGTCC 11 GTGCTTCTCTGGTCCTCAAGAGACT NONO 200057_s_at 12 GCCCCAGAGAAACTGCCACATACAC gccccagagaaactgccacatacaccacaaaaaccaaacatgccccaatgacc NM_007363.2 ttagccccattgctccattcactcccaggtgagaattcaggcaaacgtccaca aaggtcacaggcagcgtacatacggttctgttataccccatatattacccctt catgtcctaaagaagacattttctcttagagattttcattttagtgtatcttt aaaaaaaaaatcttgtgttaacttgcctccatctttttcttggggtgagggac accagggaatgacccttttgtgtctatgatgttgctgttcacagcttttcttg ataggcctagtacaatcttgggaacagggttactgtatactgaaggtctgaca gtagctcttagactcgcctatcttaggtagtcatgctgtgcattttttttttcattggt gtactgtgtttgatttgtctca 13 GCTCCATTCACTCCCAGGTGAGAAT 14 GGCAAACGTCCACAAAGGTCACAGG 15 AGGTCACAGGCAGCGTACATACGGT 16 CATACGGTTCTGTTATACCCCATAT 17 TATTACCCCTTCATGTCCTAAAGAA 18 AAATCTTGTGTTAACTTGCCTCCAT 19 GGAATGACCCTTTTGTGTCTATGAT 20 CACAGCTTTTCTTGATAGGCCTAGT 21 TGACAGTAGCTCTTAGACTCGCCTA 22 GGTGTACTGTGTTTGATTTGTCTCA RNPS1 200060_s_at 23 CAGGGAAAAGTGAGGCTCTTGGGGG cagggaaaagtgaggctcttgggggtggtttgaccctgcttacctgggagcac BC001659.1 acttttcccttccccgatgacctgggatggtggccaggccgtgcccttgctgt tgctgggcagtgtccttttggaaagggagctgccccaggctttagtgcagctg ccaaccctgttaggcctggcctctcgaggcctcttctgatctcaagggtcaca ccccctcaaagatcctctcacccatggtagttgctgctcgtggttctgtctgt ccgtgcaccgatgcacacaccgcaccccaccactgtactctgaaattggcgag tgagtggagagccagctctgcggagtcatcacgcagccatggttgtgcctgcc gttcatggtggtctttcaggttatcttggcaacatgtacattgcttttatttt ttttcttttttgctttcattgtacagtcagtactataaaatttctcttttgagtttta tacctttgtagcattttagatgacattgtgtttgtactttgttg 24 TTACCTGGGAGCACACTTTTCCCTT 25 CCTTCCCCGATGACCTGGGATGGTG 26 CCCCGATGACCTGGGATGGTGGCCA 27 CCCACCACTGTACTCTGAAATTGGC 28 CACTGTACTCTGAAATTGGCGAGTG 29 CCGTTCATGGTGGTCTTTCAGGTTA 30 GGTGGTCTTTCAGGTTATCTTGGCA 31 GGTCTTTCAGGTTATCTTGGCAACA 32 TCAGGTTATCTTGGCAACATGTACA 33 ATGACATTGTGTTTGTACTTTGTTG HSP90AB1 200064_at 34 AATAGACTTGTGTCTTCACCTTGCT aatagacttgtgtcttcaccttgctgcattgtgaccagcacctacggctggac AF275719.1 agccaatatggagcggatcatgaaagcccaggcacttcgggacaactccacca tgggctatatgatggccaaaaagcacctggagatcaaccctgaccaccccatt gtggagacgctgcggcagaaggctgaggccgacaagaatgataaggcagttaa ggacctggtggtgctgctgtttgaaaccgccctgctatcttctggcttttccc ttgaggatccccagacccactccaaccgcatctatcgcatgatcaagctaggt ctaggtattgatgaagatgaagtggcagcagaggaacccaatgctgcagttcc tgatgagatcccccctctcgagggcgatgaggatgcgtctcgcatggaagaagtcgat taggttaggagttcatagttggaaaacttgtgcccttgtatagtgtccc 35 GTCTTCACCTTGCTGCATTGTGACC 36 GTGACCAGCACCTACGGCTGGACAG 37 GAGCGGATCATGAAAGCCCAGGCAC 38 AAAAGCACCTGGAGATCAACCCTGA 39 TGGTGGTGCTGCTGTTTGAAACCGC 40 CAACCGCATCTATCGCATGATCAAG 41 GCAGAGGAACCCAATGCTGCAGTTC 42 TCCCCCCTCTCGAGGGCGATGAGGA 43 GGGCGATGAGGATGCGTCTCGCATG 44 AACTTGTGCCCTTGTATAGTGTCCC SLC25A5 200657_at 45 TAACACAATCTTGAGCATTCTTGAC cctacttcggtatctatgacactgcaaagggaatgcttccggatcccaagaac NM_001152.1 actcacatcgtcatcagctggatgatcgcacagactgtcactgctgttgccgg gttgacttcctatccatttgacaccgttcgccgccgcatgatgatgcagtcag ggcgcaaaggaactgacatcatgtacacaggcacgcttgactgctggcggaag attgctcgtgatgaaggaggcaaagcttttttcaagggtgcatggtccaatgt tctcagaggcatgggtggtgcttttgtgcttgtcttgtatgatgaaatcaaga agtacacataagttatttcctaggatttttccccctgtgaacaggcatgttgt attctataacacaatcttgagcattcttgacagactcctggctgtcagtttctcagtg gcaac 46 CATTCTTGACAGACTCCTGGCTGTC 47 TGGCTGTCAGTTTCTCAGTGGCAAC 48 CCTACTTCGGTATCTATGACACTGC 49 GGGAATGCTTCCGGATCCCAAGAAC 50 CAAGAACACTCACATCGTCATCAGC 51 ATGATCGCACAGACTGTCACTGCTG 52 GCTGGCGGAAGATTGCTCGTGATGA 53 GGGTGCATGGTCCAATGTTCTCAGA 54 GAGGCATGGGTGGTGCTTTTGTGCT 55 TGCTTTTGTGCTTGTCTTGTATGAT GRN 200678_x_at 56 CGTAGCCCTCACGTGGGTGTGAAGG cgtagccctcacgtgggtgtgaaggacgtggagtgtggggaaggacacttctg NM_002087.1 ccatgataaccagacctgctgccgagacaaccgacagggctgggcctgctgtc cctaccgccagggcgtctgttgtgctgatcggcgccactgctgtcctgctggc ttccgctgcgcagccaggggtaccaagtgtttgcgcagggaggccccgcgctg ggacgcccctttgagggacccagccttgagacagctgctgtgagggacagtac tgaagactctgcagccctcgggaccccactcggagggtgccctctgctcaggc ctccctagcacctccccctaaccaaattctccctggaccccattctgagctcc ccatcaccatgggaggtggggcctcaatctaaggccttccctgtcagaagggg gttgtggcaaaagccacattacaagctgccatcccctccccgtttcagtggac cctgtggccaggtgcttttccctatccacaggggtgtttgtgtgtgtgcgcgtgtgc gtttcaata 57 GAAGGACACTTCTGCCATGATAACC 58 TGCCATGATAACCAGACCTGCTGCC 59 GCCGAGACAACCGACAGGGCTGGGC 60 GCCAGGGGTACCAAGTGTTTGCGCA 61 GACCCAGCCTTGAGACAGCTGCTGT 62 CAGTACTGAAGACTCTGCAGCCCTC 63 TGAGCTCCCCATCACCATGGGAGGT 64 TGGGGCCTCAATCTAAGGCCTTCCC 65 AAAGCCACATTACAAGCTGCCATCC 66 GTGTGTGCGCGTGTGCGTTTCAATA CCND2 200953_s_at 67 GCCATTACAGTATCCAATGTCTTTT gccattacagtatccaatgtcttttgacaggtgcctgtccttgaaaaacaaag NM_001759.1 tttctatttttatttttaattggtttagttcttaactgctggccaactcttac atccccagcaaatcatcgggccattggattttttccattatgttcatcaccct tatatcatgtacctcagatctctctctctctcctctctctcagttatatagtt tcttgtcttggactttttttttcttttctttttctttttttttttgctttaaa acaagtgtgatgccatatcaagtccatgttattctctcacagtgtactctata agaggtgtgggtgtctgtttggtcaggatgttagaaagtgctgataagtagca tgatcagtgtatgcgaaaaggtttttaggaagtatggcaaaaatgttgtattg gctatgatggtgacatgatatagtcagctgccttttaagaggtcttatctgttcagtg tt 68 GTTTAGTTCTTAACTGCTGGCCAAC 69 CTTACATCCCCAGCAAATCATCGGG 70 TATGTTCATCACCCTTATATCATGT 71 TTATATCATGTACCTCAGATCTCTC 72 TCTCCTCTCTCTCAGTTATATAGTT 73 GTGTGATGCCATATCAAGTCCATGT 74 AGTCCATGTTATTCTCTCACAGTGT 75 GGTGTGGGTGTCTGTTTGGTCAGGA 76 ATGTTGTATTGGCTATGATGGTGAC 77 TAAGAGGTCTTATCTGTTCAGTGTT TXNIP 201010_s_at 78 GTGTTCTCCTACTGCAAATATTTTC gtgttctcctactgcaaatattttcatatgggaggatggttttctcttcatgt NM_006472.1 aagtccttggaattgattctaaggtgatgttcttagcactttaattcctgtca aattttttgttctccccttctgccatcttaaatgtaagctgaaactggtctac tgtgtctctagggttaagccaaaagacaaaaaaaattttactacttttgagat tgccccaatgtacagaattatataattctaacgcttaaatcatgtgaaagggt tgctgctgtcagccttgcccactgtgacttcaaacccaaggaggaactcttga tcaagatgcccaaccctgtgatcagaacctccaaatactgccatgagaaacta gagggcaggtgttcataaaagccctttgaacccccttcctgccctgtgttagg agatagggatattggcccctcactgcagctgccagcacttggtcagtcactct cagccatagcactttgttcactgtcctgtgtcagagcactgagctccacccttttctg agagttat 79 GGTTTTCTCTTCATGTAAGTCCTTG 80 TGTTCTTAGCACTTTAATTCCTGTC 81 GCTGAAACTGGTCTACTGTGTCTCT 82 GAAAGGGTTGCTGCTGTCAGCCTTG 83 CAACCCTGTGATCAGAACCTCCAAA 84 AGATAGGGATATTGGCCCCTCACTG 85 CACTCTCAGCCATAGCACTTTGTTC 86 ACTTTGTTCACTGTCCTGTGTCAGA 87 TGTGTCAGAGCACTGAGCTCCACCC 88 AGCTCCACCCTTTTCTGAGAGTTAT RBBP7 201092_at 89 GCAGAAGATGGGCCTCCAGAACTCC gcagaagatgggcctccagaactcctgtttattcatggaggacacactgctaa NM_002893.2 gatttcagattttagctggaaccccaatgagccttgggtcatttgctcagtgt ctgaggataacatcatgcagatatggcaaatggctgaaaatatttacaatgat gaagagtcagatgtcacgacatccgaactggagggacaaggatcttaaaccca aagtacgagaaatgtttctgttgaatgtaatgctacatgaatgcttgatttat caagcgccaaaaaggcattgtatagtaggaaatgtaagtggggtggcttatgg cttctttatcctctgattctagcactttcaagtgagctgttgcgtactgtatc atattgtagctattagggaagagaagaatgttgcttaagaaagaacatcacca ttgattttaaatacaagtagcagggtattgcctttgattcaactgttttaagtcctca ttttctcaaactaagtgcttgctgtt 90 TATTCATGGAGGACACACTGCTAAG 91 TTAGCTGGAACCCCAATGAGCCTTG 92 AGCCTTGGGTCATTTGCTCAGTGTC 93 GTCACGACATCCGAACTGGAGGGAC 94 TGGGGTGGCTTATGGCTTCTTTATC 95 TTATCCTCTGATTCTAGCACTTTCA 96 GTGAGCTGTTGCGTACTGTATCATA 97 GTAGCAGGGTATTGCCTTTGATTCA 98 CAACTGTTTTAAGTCCTCATTTTCT 99 TTTCTCAAACTAAGTGCTTGCTGTT LGALS1 201105_at 100 AAACCTGGAGAGTGCCTTCGAGTGC ctcctggactcaatcatggcttgtggtctggtcgccagcaacctgaatctcaa NM_002305.2 acctggagagtgccttcgagtgcgaggcgaggtggctcctgacgctaagagct tcgtgctgaacctgggcaaagacagcaacaacctgtgcctgcacttcaaccct cgcttcaacgcccacggcgacgccaacaccatcgtgtgcaacagcaaggacgg cggggcctgggggaccgagcagcgggaggctgtctttcccttccagcctggaa gtgttgcagaggtgtgcatcaccttcgaccaggccaacctgaccgtcaagctg ccagatggatacgaattcaagttccccaaccgcctcaacctggaggccatcaactaca tggcagctgacggtgacttcaa 101 GTGCCTTCGAGTGCGAGGCGAGGTG 102 CTCCTGACGCTAAGAGCTTCGTGCT 103 GCTTCGTGCTGAACCTGGGCAAAGA 104 TGTGCAACAGCAAGGACGGCGGGGC 105 ACCGAGCAGCGGGAGGCTGTCTTTC 106 GACCGTCAAGCTGCCAGATGGATAC 107 ACATGGCAGCTGACGGTGACTTCAA 108 CTCCTGGACTCAATCATGGCTTGTG 109 ATCATGGCTTGTGGTCTGGTCGCCA 110 GTCGCCAGCAACCTGAATCTCAAAC ITPR3 201189_s_at 111 ACAGTCCTGCTTAGAGCCCTTAAAA acagtcctgcttagagcccttaaaaagacttgaaagttcactgggactcagtt NM_002224.1 taccttaatgccttagcagaagataaatcctacctagagacctttgttcctta aagcaataactgacaactctttgtagtcctccttgtgggtagttaagagtggg gtcacccctttaactccaagcactacattttggcggctgcggcctctggggga ggtggcagttatgctgttactagtgattttagggctttgttatttaacttatt tcaagggtgctgtgctcagccctgcccatggctgtgcagctccctccgtgcct cagatctgctgtagccagtgcagacctcactgtcgtgtccatgccacccccgg catggctccaggtggcctggtgactccatgatggacgatcttgctcccaggac ctgcctcttcccaggcttcctggggaagagttgtacgcccaggcaacaagggctgag ctgcgcttgcgtggctgtttcatgaccgc 112 GGACTCAGTTTACCTTAATGCCTTA 113 TAAATCCTACCTAGAGACCTTTGTT 114 AACTGACAACTCTTTGTAGTCCTCC 115 GGGAGGTGGCAGTTATGCTGTTACT 116 TGCCTCAGATCTGCTGTAGCCAGTG 117 GCTGTAGCCAGTGCAGACCTCACTG 118 CTCCAGGTGGCCTGGTGACTCCATG 119 CCATGATGGACGATCTTGCTCCCAG 120 GGGGAAGAGTTGTACGCCCAGGCAA 121 GCTTGCGTGGCTGTTTCATGACCGC SPCS2 201240_s_at 122 GTATAGCTTTGGGCCATGTAGCATT gagaagttgtagctctgatgtctagctgtagtctccttgatctgctgattgca NM_014752.1 ttattttaatttgcttttctgggaaagcagttttgctaaaagctgtacagact ttttcttttgtacctagcagtactttatatagtatagctttgggccatgtagc attttaagactcaattttaaaaaattattaatctgttgctgactcttaattcc tatttcaatatgtgtttccttgaagaattcaggatacaacttcttgtgtatga cagctttccttcacacactatttttgtgggtgtgtatatatctgatttgggaa gaatttaaaaaacacatagctttttaatttgtttgaaacagactttctgcctg ttacatttttgcttttaaccaattaaagaagccaatggcattttagttttatattgt gttttccactagtatatccctgttgatttgtttgtgccttt 123 AAATTATTAATCTGTTGCTGACTCT 124 GTTGCTGACTCTTAATTCCTATTTC 125 GTGTATGACAGCTTTCCTTCACACA 126 TCCTTCACACACTATTTTTGTGGGT 127 GACTTTCTGCCTGTTACATTTTTGC 128 GTGTTTTCCACTAGTATATCCCTGT 129 TCCCTGTTGATTTGTTTGTGCCTTT 130 GAGAAGTTGTAGCTCTGATGTCTAG 131 GATGTCTAGCTGTAGTCTCCTTGAT 132 GTCTCCTTGATCTGCTGATTGCATT TMEM109 201361_at 133 GAGCAGTCACTCTCAGAATCTTGAT gagcagtcactctcagaatcttgattccccatcagccaaagcaaaagatggct NM_024092.1 gctgctttgtaggcatgtgcctgcaagtgggaccttgctgggcattatatgcc ctgtgggggtttcagagaccctgaaagaggagggaggacccgcctccttgtct gcacaactgcatgcacttctctccccatcgctccacaacctgaaaccgagaag gagttgctgaccagtgcccaccccggcagcccgggaggaacacaggcagctcc tttcccttcacgtggtctgcagagagcagggtgagctgccagctgcccctctc caccagggtaccctgtcttggtggttaggggccacttttcctttgaggctcta gtggaggtggatgtccttctctgccaggcttggcacatgatgtgaagaataaatgcc caattcttactgttcaggt 134 TCAGAATCTTGATTCCCCATCAGCC 135 AAGTGGGACCTTGCTGGGCATTATA 136 ATGCCCTGTGGGGGTTTCAGAGACC 137 TCTGCACAACTGCATGCACTTCTCT 138 TCGCTCCACAACCTGAAACCGAGAA 139 AGAAGGAGTTGCTGACCAGTGCCCA 140 AGCCCGGGAGGAACACAGGCAGCTC 141 CTCCACCAGGGTACCCTGTCTTGGT 142 TAGTGGAGGTGGATGTCCTTCTCTG 143 AATGCCCAATTCTTACTGTTCAGGT IFI30 201422_at 144 TGGAGGCCTGCGTGTTGGATGAACT tggaggcctgcgtgttggatgaacttgacatggagctagccttcctgaccatg NM_006332.1 tctggcatggcatggaagagtttgaggacatggagagaagtctgccactatgc ctgcagctctacgccccagggctgtcgccagaactatcatggagtgtgcaatg ggggaccgcggcatgcagctcatgcacgccaacgcccagcggacagatgctct ccagccaccgcacgagtatgtgccctgggtcaccgtcaatgggaaacccttgg aagatcagacccagctccttacccttgtctgccagttgtaccagggcaagaag ccggatgtctgcccttcctcaaccagctccctccggagtgtttgcttcgagtg ttggccggtgggctgcggagagctcatggaaggcgagtgggaactcggctgcc tgcctttttttctgatccagaccctcggcacctgctacttaccaactggaaaa ttttatgcatcccatgaagcccagatacacaaaattccacccctagatcaagaatcct gctccacta 145 TTGACATGGAGCTAGCCTTCCTGAC 146 CAGGGCTGTCGCCAGAACTATCATG 147 TGGAGTGTGCAATGGGGGACCGCGG 148 TCCAGCCACCGCACGAGTATGTGCC 149 TGCCCTGGGTCACCGTCAATGGGAA 150 CCTTGTCTGCCAGTTGTACCAGGGC 151 GGCAAGAAGCCGGATGTCTGCCCTT 152 GGAGTGTTTGCTTCGAGTGTTGGCC 153 ATGCATCCCATGAAGCCCAGATACA 154 CTAGATCAAGAATCCTGCTCCACTA CAT 201432_at 155 TTAGCGTTCATCCGTGTAACCCGCT ttagcgttcatccgtgtaacccgctcatcactggatgaagattctcctgtgct NM_001752.1 agatgtgcaaatgcaagctagtggcttcaaaatagagaatcccactttctata gcagattgtgtaacaattttaatgctatttccccaggggaaaatgaaggttag gatttaacagtcatttaaaaaaaaaatttgttttgacggatgattggattatt catttaaaatgattagaaggcaagtttctagctagaaatatgattttatttga caaaatttgttgaaattatgtatgtttacatatcacctcatggcctattatat taaaatatggctataaatatataaaaagaaaagataaagatgatctactcaga aatttttatttttctaaggttctcataggaaaagtacatttaatacagcagtgtcatc agaagataacttgagcaccgtcatggcttaatgtttatt 156 GTAACCCGCTCATCACTGGATGAAG 157 GATGAAGATTCTCCTGTGCTAGATG 158 GATTCTCCTGTGCTAGATGTGCAAA 159 GTGCAAATGCAAGCTAGTGGCTTCA 160 GAGAATCCCACTTTCTATAGCAGAT 161 CAATTTTAATGCTATTTCCCCAGGG 162 GTATGTTTACATATCACCTCATGGC 163 TATCACCTCATGGCCTATTATATTA 164 GATAACTTGAGCACCGTCATGGCTT 165 GCACCGTCATGGCTTAATGTTTATT G3BP 201503_at 166 AAAACCCAGATAACAACCAGAGCAA aaaacccagataacaaccagagcaaaactgttgtgccttctatttatctttga BG500067 tttcagtcttggcaattgtttaaaaaaaaaatctagatttgttttattaggtt cagagtatgtggggaattatagaatccctctttcatcactttgtgtatgtctt ttgttaacatatttgttatgccttattctaaaattgagtctcaaactggaatg cctttgaagacagatgcttctatagaggttctttgacctaaatagttcagcat ttgtatttttattctggtatctaatcagattcctaatcatagcccgtaagaag gaatgttactttaatattggactttgctcatgtgctcgtgtccgcattttttt ttttncttaaaatcatagccatatggtaaattttctattttgttatggttctctttta ttgatgggcatgcagtgggtgttacttgga 167 GCAAAACTGTTGTGCCTTCTATTTA 168 TTATCTTTGATTTCAGTCTTGGCAA 169 CATATTTGTTATGCCTTATTCTAAA 170 TTGAGTCTCAAACTGGAATGCCTTT 171 GACAGATGCTTCTATAGAGGTTCTT 172 GGTTCTTTGACCTAAATAGTTCAGC 173 CAGATTCCTAATCATAGCCCGTAAG 174 TGCTCGTGTCCGCATTTTTTTTTTT 175 GGTTCTCTTTTATTGATGGGCATGC 176 GGGCATGCAGTGGGTGTTACTTGGA ARF5 201526_at 177 GCAGTGCTGCTGGTATTTGCCAACA gcagtgctgctggtatttgccaacaagcaggacatgcccaacgccatgcccgt NM_001662.2 gagcgagctgactgacaagctggggctacagcacttacgcagccgcacgtggt atgtccaggccacctgtgccacccaaggcacaggtctgtacgatggtctggac tggctgtcccacgagctgtcaaagcgctaaccagccaggggcaggcccctgat gcccggaagctcctgcgtgcatccccgggatgaccagactcccggactcctca ggcagtgccctttcctcccacttttcctcccccatagccacaggcctctgctc ctgctcctgcctgcatgttctctctgttgttggagcctggagccttgctctct gggcacagaggggtccactctcctgcctgctgggacctatggaaggggcttcc tggccaaggccccctcttccagaggaggagcagggatctgggtttcctttttttttt ctgttttgggtgtactctaggggccaggttggga 178 TGCCCGTGAGCGAGCTGACTGACAA 179 TGCCACCCAAGGCACAGGTCTGTAC 180 GTACGATGGTCTGGACTGGCTGTCC 181 TCCCACGAGCTGTCAAAGCGCTAAC 182 CTGCGTGCATCCCCGGGATGACCAG 183 TCTCTGTTGTTGGAGCCTGGAGCCT 184 GCCTTGCTCTCTGGGCACAGAGGGG 185 GCCTGCTGGGACCTATGGAAGGGGC 186 GCCCCCTCTTCCAGAGGAGGAGCAG 187 GTGTACTCTAGGGGCCAGGTTGGGA DUSP3 201536_at 188 GATTTAGCTCTTAGTTCTTCAAGTA gatttagctcttagttcttcaagtaaaattaaagtctcttgtgtaagagccaa AL048503 cacatgcccagctgcggatgggagctgttcctggacagccttctactgcctgg gaagtgatggaacaggaactcagggtgcccttaccccctccccagacctgttc cctttctttgactgacagagcaccatccaggcaaaattagagcgccaaatggt tttcttctcaatcttaaagcagtatacctttccacaggctcgtctgtgtccct gccactctgagttatccagaaaccaccacctacaaatgaggggactcatctag aagacctctaaggtccccttttggctctgaggggtctctaataatccccactt ggaattcagcaccgcaaggaaattatgggtatgtgagccataatatgatggcc agcaggtngcgctgccttccacccatggtgatggatggtttggaaagggaatgttggt gccttttgtgccaca 189 GAACAGGAACTCAGGGTGCCCTTAC 190 TGACTGACAGAGCACCATCCAGGCA 191 AAAGCAGTATACCTTTCCACAGGCT 192 TCCCTGCCACTCTGAGTTATCCAGA 193 GAAACCACCACCTACAAATGAGGGG 194 AGGGGACTCATCTAGAAGACCTCTA 195 CCTTTTGGCTCTGAGGGGTCTCTAA 196 GGGTCTCTAATAATCCCCACTTGGA 197 CCCACTTGGAATTCAGCACCGCAAG 198 GAATGTTGGTGCCTTTTGTGCCACA ID2 201565_s_at 199 GAAAAACAGCCTGTCGGACCACAGC gaaaaacagcctgtcggaccacagcctgggcatctcccggagcaaaacccctg NM_002166.1 tggacgacccgatgagcctgctatacaacatgaacgactgctactccaagctc aaggagctggtgcccagcatcccccagaacaagaaggtgagcaagatggaaat cctgcagcacctcatcgactacatcttggacctgcagatcgccctggactcgc atcccactattgtcagcctgcatcaccagagacccgggcagaaccagcgctcc aggacgccgctgaccaccctcaacacggatatcagcatcctgtccttgcaggc ttctgaattcccttctgagttaatgtcaaatgacagcaaagcactgtgtggct gaataagcggtgttcatgatttcttttattctttgcacaacaacaacaacaacaaattc acggaatcttttaagtgctgaac 200 GACCCGATGAGCCTGCTATACAACA 201 CCCGATGAGCCTGCTATACAACATG 202 GAGCCTGCTATACAACATGAACGAC 203 TATACAACATGAACGACTGCTACTC 204 GTGTGGCTGAATAAGCGGTGTTCAT 205 GAATAAGCGGTGTTCATGATTTCTT 206 AGCGGTGTTCATGATTTCTTTTATT 207 GGTGTTCATGATTTCTTTTATTCTT 208 CAACAACAAATTCACGGAATCTTTT 209 TCACGGAATCTTTTAAGTGCTGAAC DNMT1 201697_s_at 210 ACCCAGAGCAGCACCGTGTGGTGAG acccagagcagcaccgtgtggtgagcgtgcgggagtgtgcccgctcccagggc NM_001379.1 ttccctgacacctaccggctcttcggcaacatcctggacaagcaccggcaggt gggcaatgccgtgccaccgcccctggccaaagccattggcttggagatcaagc tttgtatgttggccaaagcccgagagagtgcctcagctaaaataaaggaggag gaagctgctaaggactagttctgccctcccgtcacccctgtttctggcaccag gaatccccaacatgcactgatgttgtgtttttaacatgtcaatctgtccgttc acatgtgtggtacatggtgtttgtggccttggctgacatgaagctgttgtgtg aggttcgcttatcaactaatgatttagtgatcaaattgtgcagtactttgtgc attctggattttaaaagttttttattatgcattatatcaaatctaccactgtatgagt 211 ACATCCTGGACAAGCACCGGCAGGT 212 CGGCAGGTGGGCAATGCCGTGCCAC 213 CCCCTGGCCAAAGCCATTGGCTTGG 214 GAGATCAAGCTTTGTATGTTGGCCA 215 AGCTGCTAAGGACTAGTTCTGCCCT 216 CAATCTGTCCGTTCACATGTGTGGT 217 GGCTGACATGAAGCTGTTGTGTGAG 218 GTGTGAGGTTCGCTTATCAACTAAT 219 GCAGTACTTTGTGCATTCTGGATTT 220 ATATCAAATCTACCACTGTATGAGT CCND3 201700_at 221 TTGCATTTGGATTGGGGTCCCTCTA ttgcatttggattggggtccctctaaaatttaatgcatgatagacacatatga NM_001760.1 gggggaatagtctagatggctcctctcagtactttggaggcccctatgtagtc cgtgctgacagctgctcctagagggaggggcctaggcctcagccagagaagct ataaattcctctttgctttgctttctgctcagcttctcctgtgtgattgacag ctttgctgctgaaggctcattttaatttattaattgctttgagcacaacttta agaggacataatgggggcctggccatccacaagtggtggtaaccctggtggtt gctgttttcctcccttctgctactggcaaaaggatctttgtggccaaggagct gctatagcctggggtggggtcatgccctcctctcccattgtccctctgcccca tcctccagcagggaaaatgcagcagggatgccctggaggtggctgagcccctg tctagagagggaggcaagccctgttgacacaggtctttcctaaggctgcaaggtttag gctggtggccc 222 GGGAATAGTCTAGATGGCTCCTCTC 223 GGCTCCTCTCAGTACTTTGGAGGCC 224 CTATGTAGTCCGTGCTGACAGCTGC 225 GCTCAGCTTCTCCTGTGTGATTGAC 226 GCTTTGCTGCTGAAGGCTCATTTTA 227 TAACCCTGGTGGTTGCTGTTTTCCT 228 TGGCCAAGGAGCTGCTATAGCCTGG 229 GGCTGAGCCCCTGTCTAGAGAGGGA 230 GACACAGGTCTTTCCTAAGGCTGCA 231 GCTGCAAGGTTTAGGCTGGTGGCCC CD14 201743_at 232 GTGCCTAAAGGACTGCCAGCCAAGC ccatccagaatctagcgctgcgcaacacaggaatggagacgcccacaggcgtg NM_000591.1 tgcgccgcactggcggcggcaggtgtgcagccccacagcctagacctcagcca caactcgctgcgcgccaccgtaaaccctagcgctccgagatgcatgtggtcca gcgccctgaactccctcaatctgtcgttcgctgggctggaacaggtgcctaaa ggactgccagccaagctcagagtgctcgatctcagctgcaacagactgaacag ggcgccgcagcctgacgagctgcccgaggtggataacctgacactggacggga atcccttcctggtccctggaactgccctcccccacgagggctcaatgaactcc ggcgtggtcccagcctgtgcacgttcgaccctgtcggtgggggtgtcgggaac cctggtgctgctccaaggggcccggggctttgcctaagatccaagacagaata atgaatggactcaaactgccttggcttcaggggagtcccgtcaggacgttgaggact tttcgaccaattcaacc 233 GCCAAGCTCAGAGTGCTCGATCTCA 234 GCAACAGACTGAACAGGGCGCCGCA 235 TGACGAGCTGCCCGAGGTGGATAAC 236 CTGACACTGGACGGGAATCCCTTCC 237 ACGAGGGCTCAATGAACTCCGGCGT 238 CCCGGGGCTTTGCCTAAGATCCAAG 239 GGGAGTCCCGTCAGGACGTTGAGGA 240 TGAGGACTTTTCGACCAATTCAACC 241 CCATCCAGAATCTAGCGCTGCGCAA 242 CCCTAGCGCTCCGAGATGCATGTGG RPA2 201756_at 243 GGTTTCATCTATCAAATGTCTCCTC gatattttacagctggacctagtttcacaatctgttgtctccagctctgcata NM_002946.1 tgtctggccagggggcttctaggaagtaggtttcatctatcaaatgtctcctc tgacttccttttgaaacttactgctcttctgttttattttgttttgtttgaag ctcagagggagatgggcaattgacagggatgcaatccagggtgggatttcttg aggaagttacaaataagcttgttacaacatcaagatagatggaattggaagga tgctaccaggagagtacttacatagtgctcaggagtttctcttcttaaaatgt ttactgctgaaagatgagcaggaccagggcgttataggcagagccctagccag aaacctgctggcctctgcctgttttcatttcccactttggttgtgtggcatta ctttcagaattgcactttcctgcttgtcatgactttttgacacacttgccatgac 244 TCCTCTGACTTCCTTTTGAAACTTA 245 ACTTACTGCTCTTCTGTTTTATTTT 246 GACAGGGATGCAATCCAGGGTGGGA 247 TAGCCAGAAACCTGCTGGCCTCTGC 248 TGTTTTCATTTCCCACTTTGGTTGT 249 ACTTTCCTGCTTGTCATGACTTTTT 250 GACTTTTTGACACACTTGCCATGAC 251 GATATTTTACAGCTGGACCTAGTTT 252 GCTGGACCTAGTTTCACAATCTGTT 253 CTCCAGCTCTGCATATGTCTGGCCA CDC25B 201853_s_at 254 GCTTGGTCTGTTTGACTTTACGCCC gcttggtctgtttgactttacgcccatctcaggacacttccgtagactgttta NM_021873.1 ggttcccctgtcaaatatcagttacccactcggtcccagttttgttgccccag aaagggatgttattatccttgggggctcccagggcaagggttaaggcctgaat catgagcctgctggaagcccagcccctactgctgtgaaccctggggcctgact gctcagaacttgctgctgtcttgttgcggatggatggaaggttggatggatgg gtggatggccgtggatggccgtggatgcgcagtgccttgcatacccaaaccag gtgggagcgttttgttgagcatgacacctgcagcaggaatatatgtgtgccta tttgtgtggacaaaaatatttacacttagggtttggagctattcaagaggaaa tgtcacagaagcagctaaaccaaggactgagcaccctctggattctgaatctc aagatgggggcagggctgtgcttgaaggccctgctgagtcatctgttagggccttgg ttc 255 CCATCTCAGGACACTTCCGTAGACT 256 GTTTAGGTTCCCCTGTCAAATATCA 257 CAAATATCAGTTACCCACTCGGTCC 258 TGAATCATGAGCCTGCTGGAAGCCC 259 CCCCTACTGCTGTGAACCCTGGGGC 260 TTGCTGCTGTCTTGTTGCGGATGGA 261 GATGGCCGTGGATGGCCGTGGATGC 262 GTGGGAGCGTTTTGTTGAGCATGAC 263 GCACCCTCTGGATTCTGAATCTCAA 264 GAGTCATCTGTTAGGGCCTTGGTTC ST6GAL1 201998_at 265 GGCTGCTTAACTGCTGTATAGGACA ggctgcttaactgctgtataggacaagccccttacccctctctgggcccatga AI743792 attcctggcttggtttatgttctgatttgacacactgattttaatcttcgaat catgacactgagtgcagaggaggtggcattccgacagcaggacatacatgttg gtgtgaagactgggacgacactgggtagaatctagtttttaattattattaat ataaaggatcaaattaatttaaatatgattctgaagtctacagaacttttagt tctgtgctgtctatgtggacactttggtaaaatgcaaattatgatatggacgt tatcattggtctggtgagatgtttcatatttgtgacagttaatttaaaaatta tganttaatgctgcctgtgtctatggggttctgtcttctttgatagccatctattcat ctggatcatgggaccctctctaa 266 TGCTGTATAGGACAAGCCCCTTACC 267 GCCCATGAATTCCTGGCTTGGTTTA 268 GGCTTGGTTTATGTTCTGATTTGAC 269 GGTGGCATTCCGACAGCAGGACATA 270 GAAGACTGGGACGACACTGGGTAGA 271 AGTTCTGTGCTGTCTATGTGGACAC 272 AATGCTGCCTGTGTCTATGGGGTTC 273 TATGGGGTTCTGTCTTCTTTGATAG 274 GATAGCCATCTATTCATCTGGATCA 275 ATCTGGATCATGGGACCCTCTCTAA ARL2BP 202092_s_at 276 GGGCCACAGTTTCAGTACTTCAGCC ccctcctggacctatttatcctgaaacaccttcttgtattcattaaccatagt NM_012106.1 actcctccccacctcaagtagacacctctctcaggagcttctgagtcagacgc ctctggagcgagccctatgtcaggcactccacctggggggcccttccccagca tacctgctggtgtgtaagtgtggactaacccgccgccaccaccctctgttcca gcaggctctgcatgaatctttgtgcacttgcacctctttttcacatgggccac agtttcagtacttcagcctcagtggggttcctgatgtttatctagggtgttac tcaagcccagtttgagattttggagtctcctgtgatcacatcttgtctcggct gtaggaatcaacagaaggagacgtcctctacataaaagctccatgtgaaaagc tactcctagtcttaacatttgcagtccttgtgtcactgtcttctggtcctgatgtag tccc 277 CTTCAGCCTCAGTGGGGTTCCTGAT 278 TTTGGAGTCTCCTGTGATCACATCT 279 TCACATCTTGTCTCGGCTGTAGGAA 280 GACGTCCTCTACATAAAAGCTCCAT 281 GCTACTCCTAGTCTTAACATTTGCA 282 TGTCTTCTGGTCCTGATGTAGTCCC 283 CCCTCCTGGACCTATTTATCCTGAA 284 ATTCATTAACCATAGTACTCCTCCC 285 GACACCTCTCTCAGGAGCTTCTGAG 286 CTCTGGAGCGAGCCCTATGTCAGGC TSPO 202096_s_at 287 GGCTCCTACCTGGTCTGGAAAGAGC ggctcctacctggtctggaaagagctgggaggcttcacagagaaggctgtggt NM_000714.2 tcccctgggcctctacactgggcagctggccctgaactgggcatggcccccca tcttctttggtgcccgacaaatgggctgggccttggtggatctcctgctggtc agtggggcggcggcngccactaccgtggcctggtaccaggtgagcccgctggc cgcccgcctgctctacccctacctggcctggctggccttcgcgaccacactca actactgcgtatggcgggacaaccatggctggcatgggggacggcggctgcca gagtgagtgcccggcccaccagggactgcagctgcaccagcaggtgccatcac gcttgtgatgtggtggccgtcacgctttcatgaccactgggcctgctagtctg tcagggccttggcccaggggtcagcagagcttcagaggttgccccacctgagc ccccacccgggagcagtgtcctgtgctttctgcatgcttagagcatg 288 GGAAAGAGCTGGGAGGCTTCACAGA 289 CATCTTCTTTGGTGCCCGACAAATG 290 CCGACAAATGGGCTGGGCCTTGGTG 291 CGTGGCCTGGTACCAGGTGAGCCCG 292 GACCACACTCAACTACTGCGTATGG 293 AACTACTGCGTATGGCGGGACAACC 294 ATGGCGGGACAACCATGGCTGGCAT 295 TGCACCAGCAGGTGCCATCACGCTT 296 TCACGCTTGTGATGTGGTGGCCGTC 297 GTGCTTTCTGCATGCTTAGAGCATG ZMYND11 202136_at 298 AGGTTTGTCAGGGTCACTCTAAAGA aggtttgtcagggtcactctaaagataaaaatgtaactaagtcttctgtgaaa BE250417 tatcatccatctaatcttgatgctgttgcagatggtggtgacacaagttaatt gacaaactactgccaaatggtgcacaatattttgtaaaaagtacccagtagcc ccatttcatacaatgtacctaaattatgcagtaacttggcatcatcgttccct ccttgttgctgtgtaattagtcagtgttgccacagtgtgtggcgctgatggag atgtcagaaccgagaacacttaaccttctttgattgtttttcaagttttaaga cttcgatccacccctatgagagcaagtaattgtggaaatatttttggtgtaaa atcattccagagtatgtaatatttaactgatagctgcatgaaagtgagattcg tgttactttggcttttctgtctctgttgacacggttgcacatttccaagtta 299 GTGAAATATCATCCATCTAATCTTG 300 TGTAAAAAGTACCCAGTAGCCCCAT 301 GTAGCCCCATTTCATACAATGTACC 302 GCAGTAACTTGGCATCATCGTTCCC 303 AGTGTGTGGCGCTGATGGAGATGTC 304 GTCAGAACCGAGAACACTTAACCTT 305 GATCCACCCCTATGAGAGCAAGTAA 306 GAGATTCGTGTTACTTTGGCTTTTC 307 GCTTTTCTGTCTCTGTTGACACGGT 308 GACACGGTTGCACATTTCCAAGTTA BLMH 202179_at 309 GCATGTCCCTGAAGAGGTGCTAGCT gcatgtccctgaagaggtgctagctgtgttagagcaggaacccattatcctgc NM_000386.1 cagcatgggaccccatgggagctttggctgagtgatactgccctccagctctt tcctccttccatggaacctgacgtagctgcaaaggacagatccagggactgaa gccaaagttatgcaagggactgtgtgttgccacaggacacagtcagatttcca gtctccaccaggaacctcttcagaaagtgtgctttatgctgaaacagaatact gttaaaggaaaaaaaagaggggggaagatcaggtcatactatctactctcctc atctctaacagctcaggatctcttagcattttaattagatgtaattgtttgtc tttaactgtcaaaaagtttggttctgtgtctgtgttttaataagacgagagga cgagcgattgaggtgtatggagagaaaacagacctaatgctccttgttcctag agtagagtggagggagggtggcctaagagttgagctctcggaactgcatgctgc 310 GAACCCATTATCCTGCCAGCATGGG 311 ACCCCATGGGAGCTTTGGCTGAGTG 312 TTTGGCTGAGTGATACTGCCCTCCA 313 TCCTCCTTCCATGGAACCTGACGTA 314 AGGAACCTCTTCAGAAAGTGTGCTT 315 TCTCCTCATCTCTAACAGCTCAGGA 316 AACAGCTCAGGATCTCTTAGCATTT 317 AAACAGACCTAATGCTCCTTGTTCC 318 GAGGGTGGCCTAAGAGTTGAGCTCT 319 TTGAGCTCTCGGAACTGCATGCTGC CTSH 202295_s_at 320 AGCCGCAGCGCAGACTGGCGGAGAA tagaacgggcatctactccagtacttcctgccataaaactccagataaagtaa NM_004390.1 accatgcagtactggctgttgggtatggagaaaaaaatgggatcccttactgg atcgtgaaaaactcttggggtccccagtggggaatgaacgggtacttcctcat cgagcgcggaaagaacatgtgtggcctggctgcctgcgcctcctaccccatcc ctctggtgtgagccgtggcagccgcagcgcagactggcggagaaggagaggaa cgggcagcctgggcctgggtggaaatcctgccctggaggaagttgtggggaga tccactgggacccccaacattctgccctcacctctgtgcccagcctggaaacc tacagacaaggaggagttccaccatgagctcacccgtgtctatgacgcaaaga tcaccagccatgtgccttagtgtccttcttaacagactcaaaccacatggacc acgaatattctttctgtccagaagggctactttccacatatagagctccagggactgt ctttt 321 TGTGGGGAGATCCACTGGGACCCCC 322 AAGGAGGAGTTCCACCATGAGCTCA 323 CTCACCCGTGTCTATGACGCAAAGA 324 AAAGATCACCAGCCATGTGCCTTAG 325 GCCTTAGTGTCCTTCTTAACAGACT 326 GGACCACGAATATTCTTTCTGTCCA 327 TGTCCAGAAGGGCTACTTTCCACAT 328 TATAGAGCTCCAGGGACTGTCTTTT 329 TAGAACGGGCATCTACTCCAGTACT 330 CAGTACTTCCTGCCATAAAACTCCA MAPRE2 202501_at 331 CAGCCACAAAACTGTCATTCACTCT cagccacaaaactgtcattcactctaggggacccctactaaagggtaacttca NM_014268.1 ggtgtgcagccctgagctccaaggctctgcaccatgccacacacttgctgtaa ggctagaagtgaagaccttattaataggagcataattgcgagggagaatcatg gttctgcagtctggtgtagacactggaataacagcacagaaaaatctatgact cccaatatcttctagaataaagaattttccctctttaacacaagggccctcct tgtcattgaccttagctaaaccatggcaattcataaatagaggaaacattaat gaattaaaagcattccttattttttaactaatatttgtacattttcttagtct ctttccaagtctttgcctcttttttttctttatttttattttttcctttgacagatg gtatcccttcctggatcattcatttcaccttggtt 332 TCATTCACTCTAGGGGACCCCTACT 333 ACTTCAGGTGTGCAGCCCTGAGCTC 334 CATGCCACACACTTGCTGTAAGGCT 335 GAATCATGGTTCTGCAGTCTGGTGT 336 AATCTATGACTCCCAATATCTTCTA 337 AACACAAGGGCCCTCCTTGTCATTG 338 CCCTCCTTGTCATTGACCTTAGCTA 339 GACCTTAGCTAAACCATGGCAATTC 340 TTGACAGATGGTATCCCTTCCTGGA 341 CTGGATCATTCATTTCACCTTGGTT ARHGEF7 202548_s_at 342 GTTACGGCATTGCCTTTTCTTTCTG gttacggcattgccttttctttctgtggatccagtatcttcctcggcttttta NM_003899.1 gggagcaggaaaaatgcgtctgagagcaactctttttaaaaacctgccctgtt gtatataactgtgtctgtttcaccgtgtgacctcccaagggggtgggaacttg atataaacgtttaaaggggccacgatttgcccgagggttactcctttgctctc accttgtatggatgaggagatgaagccatttcttatcctgtagatgtgaagca ctttcagttttcagcgatgttggaatgtagcatcagaagctcgttccttcaca ctcagtggcgtctgtgcttgtccacatgcactgggcgtctgggaccttgaatg cctgccctggttgtgtggactccttaatgccaatcatttcttcacttctctgggaca cccagggcgcctgttgacaagtg 343 TTCTGTGGATCCAGTATCTTCCTCG 344 ATCTTCCTCGGCTTTTTAGGGAGCA 345 AAACCTGCCCTGTTGTATATAACTG 346 AACTGTGTCTGTTTCACCGTGTGAC 347 GCCACGATTTGCCCGAGGGTTACTC 348 CCTTTGCTCTCACCTTGTATGGATG 349 GATGAAGCCATTTCTTATCCTGTAG 350 GTAGCATCAGAAGCTCGTTCCTTCA 351 CACACTCAGTGGCGTCTGTGCTTGT 352 CACCCAGGGCGCCTGTTGACAAGTG KIFAP3 203333_at 353 CCACCAAGCCACAAGAGACGTCATA ccaccaagccacaagagacgtcataatcaaggaaacacaggctccagcatatc NM_014970.1 tcatagacctaatgcatgataagaataatgaaatccgaaaggtctgtgataat acattagatattatagcggaatatgatgaagaatgggctaagaaaattcagag tgaaaagtttcgctggcataactctcagtggctggagatggtagagagtcgtc agatggatgagagtgagcagtacttgtatggtgatgatcgaattgagccatac attcatgaaggagatattctcgaaagacctgaccttttctacaactcagatgg attaattgcctctgaaggagccataagtcccgatttcttcaatgattaccacc ttcaaaatggagatgttgttgggcagcattcatttcctggcagccttggaatg gatggctttggccaaccagttggcattcttggacgccctgccacagcatatgg attccgccctgatgaaccttactactatggctatggatcttgataaagtatctgtttc catgtgtaatctca 354 AACACAGGCTCCAGCATATCTCATA 355 GTTTCGCTGGCATAACTCTCAGTGG 356 CTCGAAAGACCTGACCTTTTCTACA 357 GGAGCCATAAGTCCCGATTTCTTCA 358 GATTTCTTCAATGATTACCACCTTC 359 GGATGGCTTTGGCCAACCAGTTGGC 360 CCCTGCCACAGCATATGGATTCCGC 361 GCATATGGATTCCGCCCTGATGAAC 362 GAACCTTACTACTATGGCTATGGAT 363 GTATCTGTTTCCATGTGTAATCTCA OFD1 203569_s_at 364 AGCAGGAGCAAGACCAGGAGTCGGC agcaggagcaagaccaggagtcggcagataagagctcaaaaaagatggtccaa NM_003611.1 gaaggctccctagtggacacgctgcaatctagtgacaaagtcgaaagtttaac aggcttttctcatgaagaactagacgactcttggtaaccatgtttgctgccca gcttctaacttacataccgtgagaagttacgtaacatttactcctttgtaaat gtttccctatcatcagacaaaactcaataaaaatgtgtgtaatccaatgtggg tttttttttccataattaattttgataccatagtgtgtgaaccaagaataatctagtc acgtgaaacctcttctccagtcatagtatt 365 CAAGAAGGCTCCCTAGTGGACACGC 366 GTGGACACGCTGCAATCTAGTGACA 367 AAGTTTAACAGGCTTTTCTCATGAA 368 GAACTAGACGACTCTTGGTAACCAT 369 CTTGGTAACCATGTTTGCTGCCCAG 370 TGTTTGCTGCCCAGCTTCTAACTTA 371 CCAGCTTCTAACTTACATACCGTGA 372 AAATGTTTCCCTATCATCAGACAAA 373 GATACCATAGTGTGTGAACCAAGAA 374 AAACCTCTTCTCCAGTCATAGTATT CEBPA 204039_at 375 AAGCTAGGTCGTGGGTCAGCTCTGA aagctaggtcgtgggtcagctctgaggatgtatacccctggtgggagagggag NM_004364.1 acctagagatctggctgtggggcgggcatggggggtgaagggccactgggacc ctcagccttgtttgtactgtatgccttcagcattgcctaggaacacgaagcac gatcagtccatccagagggaccggagttatgacaagcttcccaaatattttgc tttatcagccgatatcaacacttgtatctggcctctgtgcccagcagtgcctt gtgcaatgtgaatgtaccgtctctgctaaaccaccattttatttggttttgtt ttgtttggttttctcggatacttgccaaaatgagactctccgtcggcagctgg gggaagggtctgagactctctttccttttggttttgggattacttttgatcct gggggaccaatgaggtgaggggggttctcctttgccctcagctttcccagccc tccggcctgggctgcccacaaggcttctcccccagaggccctggctcctggtcgggaa gggag 376 AGCTCTGAGGATGTATACCCCTGGT 377 GAGGGAGACCTAGAGATCTGGCTGT 378 AGCCTTGTTTGTACTGTATGCCTTC 379 ATGCCTTCAGCATTGCCTAGGAACA 380 GAACACGAAGCACGATCAGTCCATC 381 TCAACACTTGTATCTGGCCTCTGTG 382 TGTGAATGTACCGTCTCTGCTAAAC 383 TGTTTGGTTTTCTCGGATACTTGCC 384 GCCAAAATGAGACTCTCCGTCGGCA 385 CCCTGGCTCCTGGTCGGGAAGGGAG CCL4 204103_at 386 TACCATGAAGCTCTGCGTGACTGTC taccatgaagctctgcgtgactgtcctgtctctcctcatgctagtagctgcct NM_002984.1 tctgctctccagcgctctcagcaccaatgggctcagaccctcccaccgcctgc tgcttttcttacaccgcgaggaagcttcctcgcaactttgtggtagattacta tgagaccagcagcctctgctcccagccagctgtggtattccaaaccaaaagaa gcaagcaagtctgtgctgatcccagtgaatcctgggtccaggagtacgtgtat gacctggaactgaactgagctgctcagagacaggaagtcttcagggaaggtca cctgagcccggatgcttctccatgagacacatctcctccatactcaggactcc tctccgcagttcctgtcccttctcttaatttaatcttttttatgtgccgtgtt attgtattaggtgtcatttccattatttatattagtttagccaaaggataagtgtcc tatggggatggtccactgtcactg 387 CTCATGCTAGTAGCTGCCTTCTGCT 388 GCTCTCAGCACCAATGGGCTCAGAC 389 TTTCTTACACCGCGAGGAAGCTTCC 390 GCTTCCTCGCAACTTTGTGGTAGAT 391 AGTCTGTGCTGATCCCAGTGAATCC 392 GACCTGGAACTGAACTGAGCTGCTC 393 TCAGGGAAGGTCACCTGAGCCCGGA 394 TCCATGAGACACATCTCCTCCATAC 395 ATCTTTTTTATGTGCCGTGTTATTG 396 CTATGGGGATGGTCCACTGTCACTG STAB1 204150_at 397 GTGACGCAGGCCCTGACAACAGTTC gtgacgcaggccctgacaacagttcctgggcccctgtggccccagggacagtt NM_015136.1 gtggttagccgtatcattgtgtgggacatcatggccttcaatggcatcatcca tgctctggccagccccctcctggcacccccacagccccaggcagtgctggcgc ctgaagccccacctgtggcggcaggcgtgggggctgtgcttgccgctggagca ctgcttggcttggtggccggagctctctacctccgtgcccgaggcaagcccac gggctttggcttctctgccttccaggcggaagatgatgctgacgacgacttct caccgtggcaagaagggaccaaccccaccctggtctctgtccccaaccctgtc tttggcagcgacaccttttgtgaacccttcgatgactcactgctggaggagga cttccctgacacccagaggatcctcacagtcaagtgacgaggctggggctgaa agcagaagcatgcacagggaggagaccacttttattgcttgtctgggtggat 398 GCCCCAGGGACAGTTGTGGTTAGCC 399 GGTTAGCCGTATCATTGTGTGGGAC 400 TGTGTGGGACATCATGGCCTTCAAT 401 TCAATGGCATCATCCATGCTCTGGC 402 CGAGGCAAGCCCACGGGCTTTGGCT 403 AGATGATGCTGACGACGACTTCTCA 404 TGGCAGCGACACCTTTTGTGAACCC 405 CACTGCTGGAGGAGGACTTCCCTGA 406 CCTGACACCCAGAGGATCCTCACAG 407 ACTTTTATTGCTTGTCTGGGTGGAT RUNX3 204197_s_at 408 ATCCATTGTCCTTGTAGTTTCTTCC atccattgtccttgtagtttcttccctcctgttctctggttatagctggtccc NM_004350.1 aggtcagcgtgggaggcacctttgggttcccagtgcccagcactttgtagtct catcccagattactaacccttcctgatcctggagaggcagggatagtaaataa attgctcttcctaccccatcccccatcccctgacaaaaagtgacggcagccgt actgagtctgtaaggcccaaagtgggtacagacagcctgggctggtaaaagta ggtccttatttacaaggctgcgttaaagttgtactaggcaaacacactgatgt aggaagcacgaggaaaggaagacgttttgatatagtgttactgtgagcctgtc agtagtgggtaccaatcttttgtgacatattgtcatgctgaggtgtgacacct gctgcactcatctgatgtaaaaccatcccagagctggcgagaggatggagctgggtg gaaactgctttgcactatcgtttgctt 409 CTGTTCTCTGGTTATAGCTGGTCCC 410 GGTCCCAGGTCAGCGTGGGAGGCAC 411 CACTTTGTAGTCTCATCCCAGATTA 412 ATCCCAGATTACTAACCCTTCCTGA 413 CAGCCGTACTGAGTCTGTAAGGCCC 414 AAGTGGGTACAGACAGCCTGGGCTG 415 TGAGCCTGTCAGTAGTGGGTACCAA 416 ACCTGCTGCACTCATCTGATGTAAA 417 TGTAAAACCATCCCAGAGCTGGCGA 418 AACTGCTTTGCACTATCGTTTGCTT IFI6 204415_at 419 TGACCTTCATGGCCGTCGGAGGAGG tgaccttcatggccgtcggaggaggactcgcagtcgccgggctgcccgcgctg NM_022873.1 ggcttcaccggcgccggcatcgcggccaactcggtggctgcctcgctgatgag ctggtctgcgatcctgaatgggggcggcgtgcccgccggggggctagtggcca cgctgcagagcctcggggctggtggcagcagcgtcgtcataggtaatattggt gccctgatgggctacgccacccacaagtatctcgatagtgaggaggatgagga gtagccagcagctcccagaacctcttcttccttcttggcctaactcttccagt taggatctagaactttgcctttttttttttttttttttttttttgagatgggt tctcactatattgtccaggctagagtgcagtggctattcacagatgcgaacat agtacactgcagcctccaactcctagcctcaagtgatcctcctgtctcaacct cccaagtaggattacaagcatgcgccgacgatgcccagaatccagaacttt 420 TGGCAGCAGCGTCGTCATAGGTAAT 421 GTCGTCATAGGTAATATTGGTGCCC 422 ATTGGTGCCCTGATGGGCTACGCCA 423 GCCACCCACAAGTATCTCGATAGTG 424 GGATGAGGAGTAGCCAGCAGCTCCC 425 TTCTTGGCCTAACTCTTCCAGTTAG 426 AACTCTTCCAGTTAGGATCTAGAAC 427 GATGCGAACATAGTACACTGCAGCC 428 ATTACAAGCATGCGCCGACGATGCC 429 GACGATGCCCAGAATCCAGAACTTT NPIP 204538_x_at 430 CCTTCCACCCTCAGCGGATGATAAT cagatgcaaaatcaccccttctgcaagaaagcctctttgcaaccgggtcagaa NM_006985.1 tggcggcagtggagcatcgtcattcttcaggattgccctactggccctacctc acagctgaaactttaaaaaacaggatgggccaccagccacctcctccaactca acaacattctataattgataactccctgagcctcaagacaccttccgagtgtc tgctcactccccttccaccctcagctctaccctcagcggatgataatctcaag acacctgcggagtgtctgctctatccccttccaccctcagcggatgataatct caagacacctcccgagtgtctgctcactccccttccaccctcagctccaccct cagcggatgataatctcaagacacctcccgagtgtgtctgctcactccccttccaccc tcagcggatgataat 431 CAGATGCAAAATCACCCCTTCTGCA 432 GCCTCTTTGCAACCGGGTCAGAATG 433 GAATGGCGGCAGTGGAGCATCGTCA 434 CATCGTCATTCTTCAGGATTGCCCT 435 TGATAACTCCCTGAGCCTCAAGACA 436 AGCTCTACCCTCAGCGGATGATAAT 437 GACACCTGCGGAGTGTCTGCTCTAT 438 TGATAATCTCAAGACACCTCCCGAG 439 GCTCCACCCTCAGCGGATGATAATC 440 AAGACACCTCCCGAGTGTGTCTGCT ADA 204639_at 441 GTGGGGCTGAGCAACATTTTTACAT gtggggctgagcaacatttttacatttattccttccaagaagaccatgatctc NM_000022.1 aatagtcagttactgatgctcctgaaccctatgtgtccatttctgcacacacg tatacctcggcatggccgcgtcacttctctgattatgtgccctggcagggacc agcgcccttgcacatgggcatggttgaatctgaaaccctccttctgtggcaacttgta ctga 442 TTTTACATTTATTCCTTCCAAGAAG 443 GACCATGATCTCAATAGTCAGTTAC 444 GTCAGTTACTGATGCTCCTGAACCC 445 TGAACCCTATGTGTCCATTTCTGCA 446 ATGTGTCCATTTCTGCACACACGTA 447 GCGTCACTTCTCTGATTATGTGCCC 448 GATTATGTGCCCTGGCAGGGACCAG 449 CAGCGCCCTTGCACATGGGCATGGT 450 TGGTTGAATCTGAAACCCTCCTTCT 451 CTCCTTCTGTGGCAACTTGTACTGA TGFBR3 204731_at 452 TGTATTTCTTACAGGCCTACAGAAA tgtatttcttacaggcctacagaaattgaaaatgaccaaaatcaggaaccaca NM_003243.1 gatttgtgcccattcctaatattttgttctgcaaattaatgtataatttgagg tgaaattcagttataaagtcaaggacgaatttgcacagtgatatatttctatg tgtatgcaagtacaagtatataatatgtcacctggcacattcattttctcagt tgaagaagagaaaatttgaaaatgtccttatgcttttagagttgcaacttaag tatatttggtagggtgagtgtttccactcaaaatatgtcaacttaaaaaaaaa taggccctttcataaaaaccaaactgtagcaagatgcaaatgcatggcaaatc tgtcggtctccagttggttatctgaatagtgtcaccaattccaccaagacagtgctga gat 453 GATTTGTGCCCATTCCTAATATTTT 454 GTCAAGGACGAATTTGCACAGTGAT 455 AAGTATATAATATGTCACCTGGCAC 456 CACCTGGCACATTCATTTTCTCAGT 457 AATGTCCTTATGCTTTTAGAGTTGC 458 TTTGGTAGGGTGAGTGTTTCCACTC 459 ATGCATGGCAAATCTGTCGGTCTCC 460 GTCGGTCTCCAGTTGGTTATCTGAA 461 GAATAGTGTCACCAATTCCACCAAG 462 AATTCCACCAAGACAGTGCTGAGAT IARS 204744_s_at 463 TTGGCCTTCGGAGCAGGAAGCTAAA ttggccttcggagcaggaagctaaagctgtttctgaatgagacccaaacgcag NM_013417.1 gaaattacagaagacatccccgtgaagactttgaatatgaagactgtgtatgt ttctgtgttaccaacaacagcagacttctagcatgtacttatcaatgttgttc ggtcagcccttccctaattacacctatcccctacacatacatgcacatagaca cacacatgaacacactgaagatatttccttcaggtgtgtgtaaaatatgctgc ttggattgaaattcaaatgggattgattagtcaagtaacttgagacctcacag taatcttcacacttaaccttagacacctatgcagtcatgttgggagcaggtta caatgttacttcagcccacagtttatttctattcttgagttcttaagtacaga agatagaagtgatttaaatggcatagtatatatatcattttctggccttttaa aatttatttgagacctcttgatgaaatggacatattatatatttctgccacctggatt ttcctggata 464 GAAGACATCCCCGTGAAGACTTTGA 465 GTTACCAACAACAGCAGACTTCTAG 466 GCAGACTTCTAGCATGTACTTATCA 467 TGAGACCTCACAGTAATCTTCACAC 468 CTTCACACTTAACCTTAGACACCTA 469 GACACCTATGCAGTCATGTTGGGAG 470 AGGTTACAATGTTACTTCAGCCCAC 471 TGTTACTTCAGCCCACAGTTTATTT 472 CATATTATATATTTCTGCCACCTGG 473 TCTGCCACCTGGATTTTCCTGGATA LCK 204891_s_at 474 GACTTGGGGAGATGGAGTTCTTGTG gacttggggagatggagttcttgtgccatagtcacatggcctatgcacatatg NM_005356.1 gactctgcacatgaatcccacccacatgtgacacatatgcaccttgtgtctgt acacgtgtcctgtagttgcgtggactctgcacatgtcttgtgcatgtgtagcc tgtgcatgtatgtcttggacactgtacaaggtacccctttctggctctcccat ttcctgagaccaccagagagaggggagaagcctgggattgacagaagcttctg cccacctacttttctttcctcagatcatccagaagttcctgaagggccaggactttat ctaatacctctgtgtgctc 475 TGGAGTTCTTGTGCCATAGTCACAT 476 TATGGACTCTGCACATGAATCCCAC 477 AATCCCACCCACATGTGACACATAT 478 ACATATGCACCTTGTGTCTGTACAC 479 TGTGTAGCCTGTGCATGTATGTCTT 480 GCATGTATGTCTTGGACACTGTACA 481 CACTGTACAAGGTACCCCTTTCTGG 482 GCCTGGGATTGACAGAAGCTTCTGC 483 GGGCCAGGACTTTATCTAATACCTC 484 CTTTATCTAATACCTCTGTGTGCTC IL10RA 204912_at 485 TAGGCCATTTGGACTCTGCCTTCAA taggccatttggactctgccttcaaacaaaggcagttcagtccacaggcatgg NM_001558.1 aagctgtgaggggacaggcctgtgcgtgccatccagagtcatctcagccctgc ctttctctggagcattctgaaaacagatattctggcccagggaatccagccat gacccccacccctctgccaaagtactcttaggtgccagtctggtaactgaact ccctctggaggcaggcttgagggaggattcctcagggttcccttgaaagcttt atttatttattttgttcatttatttattggagaggcagcattgcacagtgaaa gaattctggatatctcaggagccccgaaattctagctctgactttgctgtttc cagtggtatgaccttggagaagtcacttatcctcttggagcctcagtttcctc atctgcagaataatgactgacttgtctaattcatagggatgtgaggttctgctgagg 486 GGCAGTTCAGTCCACAGGCATGGAA 487 CTGGCCCAGGGAATCCAGCCATGAC 488 AGTACTCTTAGGTGCCAGTCTGGTA 489 GTAACTGAACTCCCTCTGGAGGCAG 490 TCAGGGTTCCCTTGAAAGCTTTATT 491 ATTCTGGATATCTCAGGAGCCCCGA 492 GGAGCCCCGAAATTCTAGCTCTGAC 493 GCTGTTTCCAGTGGTATGACCTTGG 494 AGAAGTCACTTATCCTCTTGGAGCC 495 ATAGGGATGTGAGGTTCTGCTGAGG FCN1 205237_at 496 GGTATCAACTGGAGTGCGGCGAAGG gagggcaaccaccagtttgctaagtacaaatcattcaaggtggctgacgaggc NM_002003.2 agagaagtacaagctggtactgggagcctttgtcgggggcagtgcgggtaat ctctaacgggccacaacaacaacttcttctccaccaaagaccaagacaatgat gtgagttcttcgaattgtgctgagaagttccagggagcctggtggtacgccga ctgtcatgcttcaaacctcaatggtctctacctcatgggaccccatgagagct atgccaatggtatcaactggagtgcggcgaaggggtacaaatatagctacaag gtgtcagagatgaaggtgcggcccgcctagacgggccaggacccctccacatg cacctgctagtggggaggccacacccacaagcgctgcgtcgtggaag 497 CCTCCACATGCACCTGCTAGTGGGG 498 ACCCACAAGCGCTGCGTCGTGGAAG 499 GAGGGCAACCACCAGTTTGCTAAGT 500 GGGCAGTGCGGGTAATTCTCTAACG 501 TTCTCTAACGGGCCACAACAACAAC 502 GTGAGTTCTTCGAATTGTGCTGAGA 503 TCCAGGGAGCCTGGTGGTACGCCGA 504 GACTGTCATGCTTCAAACCTCAATG 505 CTCAATGGTCTCTACCTCATGGGAC 506 ATGGGACCCCATGAGAGCTATGCCA IL2RB 205291_at 507 GACAAGCGTTGAGCCACTAAGCAGA gacaagcgttgagccactaagcagaggaccttgggttcccaatacaaaaatac NM_000878.1 ctactgctgagagggctgctgaccatttggtcaggattcctgttgcctttata tccaaaataaactcccctttcttgaggttgtctgagtcttgggtctatgcctt gaaaaaagctgaattattggacagtctcacctcctgccatagggtcctgaatg tttcagaccacaaggggctccacacctttgctgtgtgttctggggcaacctac taatcctctctgcaagtcggtctccttatccccccaaatggaaattgtatttg ccttctccactttgggaggctcccacttcttgggagggttacattttttaagt cttaatcatttgtgacatatgtatctatacatccgtatcttttaatgatccgtgtgta ccatctttgtgat 508 TAAGCAGAGGACCTTGGGTTCCCAA 509 TGAGAGGGCTGCTGACCATTTGGTC 510 GATTCCTGTTGCCTTTATATCCAAA 511 CTTTCTTGAGGTTGTCTGAGTCTTG 512 CTGAGTCTTGGGTCTATGCCTTGAA 513 AATTATTGGACAGTCTCACCTCCTG 514 CCTCCTGCCATAGGGTCCTGAATGT 515 TTTGCTGTGTGTTCTGGGGCAACCT 516 GGAAATTGTATTTGCCTTCTCCACT 517 GATCCGTGTGTACCATCTTTGTGAT GNA15 205349_at 518 AACGGCCATTTGGGATGCCAGGGTG aacggccatttgggatgccagggtggatgaaaaggtgaagaaatcaggggatt NM_002068.1 gagacttgggtgggtgggcatctctcaggagccccatctccgggcgtgtcacc tcctgggcagggttctgggaccctctgtgggtgacgcacaccctgggatgggg ctagtagagccttcaggcgccttcgggcgtggactctggcgcactctagtgga caggagaaggaacgccttccaggaacctgtggactaggggtgcagggacttcc ctttgcaaggggtaacagaccgctggaaaacactgtcactttcagagctcggt ggctcacagcgtgtcctgccccggtttgcggacgagagaaatcgcggcccaca agcatcccccatcccttgcaggctgggggctgggcatgctgcatcttaaccttttgta tttat 519 GAGACTTGGGTGGGTGGGCATCTCT 520 TGACGCACACCCTGGGATGGGGCTA 521 GGGCTAGTAGAGCCTTCAGGCGCCT 522 ACTCTGGCGCACTCTAGTGGACAGG 523 GAACGCCTTCCAGGAACCTGTGGAC 524 CTAGGGGTGCAGGGACTTCCCTTTG 525 CAGACCGCTGGAAAACACTGTCACT 526 AACACTGTCACTTTCAGAGCTCGGT 527 GCGGACGAGAGAAATCGCGGCCCAC 528 CTGCATCTTAACCTTTTGTATTTAT GZMA 205488_at 529 CAGCCACACGCGAAGGTGACCTTAA cagccacacgcgaaggtgaccttaaacttttacagctgacggaaaaagcaaaa NM_006144.2 attaacaaatatgtgactatccttcatctacctaaaaagggggatgatgtgaa accaggaaccatgtgccaagttgcagggtgggggaggactcacaatagtgcat cttggtccgatactctgagagaagtcaatatcaccatcatagacagaaaagtc tgcaatgatcgaaatcactataattttaaccctgtgattggaatgaatatggt ttgtgctggaagcctccgaggtggaagagactcgtgcaatggagattctggaa gccctttgttgtgcgagggtgttttccgaggggtcacttcctttggccttgaa aataaatgcggagaccctcgtgggcctggtgtctatattcttctctcaaagaaacacc tcaactgga 530 GACCTTAAACTTTTACAGCTGACGG 531 TATGTGACTATCCTTCATCTACCTA 532 GGAACCATGTGCCAAGTTGCAGGGT 533 GACTCACAATAGTGCATCTTGGTCC 534 GCATCTTGGTCCGATACTCTGAGAG 535 TGCTGGAAGCCTCCGAGGTGGAAGA 536 TGTTGTGCGAGGGTGTTTTCCGAGG 537 AATAAATGCGGAGACCCTCGTGGGC 538 CTGGTGTCTATATTCTTCTCTCAAA 539 CTCTCAAAGAAACACCTCAACTGGA KLRK1 205821_at 540 AGGCAATTCAGATATCCCCAAGGCT aggcaattcagatatccccaaggctgcctctcccaccacaagcccagagtgga NM_007360.1 tgggctgggggaggggtgctgttttaatttctaaaggtaggaccaacacccag gggatcagtgaaggaagagaaggccagcagatcagtgagagtgcaaccccacc ctccacaggaaattgcctcatgggcagggccacagcagagagacacagcatgg gcagtgccttccctgcctgtgggggtcatgctgccacttttaatgggtcctcc acccaacggggtcagggaggtggtgctgccccagtgggccatgattatcttaa aggcattattctccagccttaagatcttaggacgtttcctttgctatgatttg tacttgcttgagtcccatgactgtttctcttcctctctttcttccttttggaa tagtaatatccatcctatgtttgtcccactattgta 541 GTAGGACCAACACCCAGGGGATCAG 542 AGATCAGTGAGAGTGCAACCCCACC 543 CACCCTCCACAGGAAATTGCCTCAT 544 AATTGCCTCATGGGCAGGGCCACAG 545 CTGCCACTTTTAATGGGTCCTCCAC 546 GGCATTATTCTCCAGCCTTAAGATC 547 GATCTTAGGACGTTTCCTTTGCTAT 548 GATTTGTACTTGCTTGAGTCCCATG 549 TTGAGTCCCATGACTGTTTCTCTTC 550 ATCCTATGTTTGTCCCACTATTGTA CD2 205831_at 551 AGACCTCGAGTTCAGCCAAAACCTC agacctcgagttcagccaaaacctccccatggggcagcagaaaactcattgtc NM_001767.1 cccttcctctaattaaaaaagatagaaactgtctttttcaataaaaagcactg tggatttctgccctcctgatgtgcatatccgtacttccatgaggtgttttctg tgtgcagaacattgtcacctcctgaggctgtgggccacagccacctctgcatc ttcgaactcagccatgtggtcaacatctggagtttttggtctcctcagagagc tccatcacaccagtaaggagaagcaatataagtgtgattgcaagaatggtaga ggaccgagcacagaaatcttagagatttcttgtcccctctcaggtcatgtgta gatgcgataaatcaagtgattggtgtgcctgggtctcactacaagcagcctatctgc 552 GGCAGCAGAAAACTCATTGTCCCCT 553 AAAAGCACTGTGGATTTCTGCCCTC 554 CTGATGTGCATATCCGTACTTCCAT 555 GTACTTCCATGAGGTGTTTTCTGTG 556 TGTGCAGAACATTGTCACCTCCTGA 557 GAGTTTTTGGTCTCCTCAGAGAGCT 558 AGAGCTCCATCACACCAGTAAGGAG 559 AATCTTAGAGATTTCTTGTCCCCTC 560 TCCCCTCTCAGGTCATGTGTAGATG 561 GTCTCACTACAAGCAGCCTATCTGC CX3CR1 205898_at 562 AGCCCCTGCCCATCTGGGAAAATAC agcccctgcccatctgggaaaataccccatcattcatgctactgccaacctgg U20350.1 ggagccagggctatgggagcagcttttttttcccccctagaaacgtttggaac aatgtaaaactttaaagctcgaaaacaattgtaataatgctaaagaaaaagtc atccaatctaaccacatcaatattgtcattcctgtattcacccgtccagacct tgttcacactctcacatgtttagagttgcaatcgtaatgtacagatggtttta taatctgatttgttttcctcttaacgttagaccacaaatagtgctcgctttct atgtagtttggtaattatcattttagaagactctaccagactgtgtattcatt gaagtcagatgtggtaactgttaaattgctgtgtatctgatagctctttggca gtctatatgtttgtataatgaatgagagaataagtcatgttccttcaagatcatgtac cccaatttacttgccattact 563 GAAAATACCCCATCATTCATGCTAC 564 GGCTATGGGAGCAGCTTTTTTTTCC 565 GTCATCCAATCTAACCACATCAATA 566 CTTGTTCACACTCTCACATGTTTAG 567 TTATAATCTGATTTGTTTTCCTCTT 568 GACCACAAATAGTGCTCGCTTTCTA 569 GTGCTCGCTTTCTATGTAGTTTGGT 570 GAAGACTCTACCAGACTGTGTATTC 571 TGTTCCTTCAAGATCATGTACCCCA 572 GTACCCCAATTTACTTGCCATTACT HK3 205936_s_at 573 AGGTCCGAGCCATCCTAGAGGATCT aggtccgagccatcctagaggatctggggctacccctgacctcagatgacgcc NM_002115.1 ctgatggtgctagaggtgtgccaggctgtgtcccagagggctgcccagctctg tggggcgggtgtagctgccgtggtggagaagatccgggggaaccggggcctgg aagagctggcagtgtctgtgggggtggatggaacgctctacaagctgcacccg cgcttctccagcctggtggcggccacagtgcgggagctggcccctcgctgtgt ggtcacgttcctgcagtcagaggatgggtccggcaaaggtgcggccctggtca ccgctgttgcctgccgccttgcgcagttgactcgtgtctgaggaaacctccag gctgaggaggtctccgccgcagccttgctggagccgggtcggggtctgcctgt ttcccagccaggcccagccacccaggactcctgggacatcccatgtgtgaccc ctctgcggccatttggccttgctccctggctttccctgagagaagtagcactcaggtt agcaatat 574 CTAGAGGATCTGGGGCTACCCCTGA 575 TGACCTCAGATGACGCCCTGATGGT 576 GACGCCCTGATGGTGCTAGAGGTGT 577 GGTGTAGCTGCCGTGGTGGAGAAGA 578 GTCTGTGGGGGTGGATGGAACGCTC 579 GATGGAACGCTCTACAAGCTGCACC 580 GGATGGGTCCGGCAAAGGTGCGGCC 581 TGACTCGTGTCTGAGGAAACCTCCA 582 GACTCCTGGGACATCCCATGTGTGA 583 GAAGTAGCACTCAGGTTAGCAATAT ING2 205981_s_at 584 GATGGATTCCAGCCAACCAGAAAGA gatggattccagccaaccagaaagatcttcaagaagaccccgcaggcagcgga NM_001564.1 ccagtgaaagccgtgatttatgtcacatggcaaatgggattgaagactgtgat gatcagccacctaaagaaaagaaatccaagtcagcaaagaaaaagaaacgctc caaggccaagcaggaaagggaagcttcacctgttgagtttgcaatagatccta atgaacctacatactgcttatgcaaccaagtgtcttatggggagatgatagga tgtgacaatgaacagtgtccaattgaatggtttcacttttcatgtgtttcact tacctataaaccaaaggggaaatggtattgcccaaagtgcaggggagataatg agaaaacaatggacaaaagtactgaaaagacaaaaaaggatagaagatcgaggtagta aaggccatccacattt 585 GGCAGCGGACCAGTGAAAGCCGTGA 586 AAAGCCGTGATTTATGTCACATGGC 587 AAGACTGTGATGATCAGCCACCTAA 588 GAAAAAGAAACGCTCCAAGGCCAAG 589 GGGAAGCTTCACCTGTTGAGTTTGC 590 GATCCTAATGAACCTACATACTGCT 591 TACTGCTTATGCAACCAAGTGTCTT 592 TTTCATGTGTTTCACTTACCTATAA 593 GGGGAAATGGTATTGCCCAAAGTGC 594 GAGGTAGTAAAGGCCATCCACATTT STAT4 206118_at 595 GCTGACATCCTGCGAGACTACAAAG gctgacatcctgcgagactacaaagttattatggctgaaaacattcctgaaaa NM_003151.1 ccctctgaagtacctatatcctgacattcccaaagacaaagccttcggtaaac actacagctctcagccttgcgaagtttcaagaccaacagaaaggggtgacaaa ggttatgttccttctgtttttatccccatctcaacaatccgaagtgattcaac agagccacattctccatcagaccttcttcccatgtctccaagtgtgtatgcgg tgttgagagaaaacctgagtcccacaacaattgaaactgcaatgaagtctcct tattctgctgaatgacaggataaactctgacgcaccaagaaaggaagcaaatg aaaaagtttaaagactgttctttgcccaataaccacattttatttcttcagct ttgtaaataccaggttctaggaaatgtttgacatctgaagctctcttcacactcccgt ggcactcctcaattgggag 596 TCCTGAAAACCCTCTGAAGTACCTA 597 GAAGTACCTATATCCTGACATTCCC 598 CAAAGCCTTCGGTAAACACTACAGC 599 GCTCTCAGCCTTGCGAAGTTTCAAG 600 TCCCCATCTCAACAATCCGAAGTGA 601 AAACCTGAGTCCCACAACAATTGAA 602 TGCAATGAAGTCTCCTTATTCTGCT 603 AGACTGTTCTTTGCCCAATAACCAC 604 GACATCTGAAGCTCTCTTCACACTC 605 TCCCGTGGCACTCCTCAATTGGGAG CD33 206120_at 606 GAGGAGCTGCATTATGCTTCCCTCA agtgggcagcaatgacacccaccctaccacagggtcagcctccccgaaacacc NM_001772.1 agaagaactccaagttacatggccccactgaaacctcaagctgttcaggtgcc gcccctactgtggagatggatgaggagctgcattatgcttccctcaactttca tgggatgaatccttccaaggacacctccaccgaatactcagaggtcaggaccc agtgaggaaccctcaagagcatcaggctcagctagaagatccacatcctctac aggtcggggaccaaaggctgattcttggagatttaactccccacaggcaatgg gtttatagacattatgtgagtttcctgctatattaacatcatcttgagacttt gcaagcagagagtcgtggaatcaaatctgtgctctttcatt 607 ATGCTTCCCTCAACTTTCATGGGAT 608 ATGAATCCTTCCAAGGACACCTCCA 609 GACACCTCCACCGAATACTCAGAGG 610 AGGAACCCTCAAGAGCATCAGGCTC 611 TAGAAGATCCACATCCTCTACAGGT 612 AGGTCGGGGACCAAAGGCTGATTCT 613 GGAATCAAATCTGTGCTCTTTCATT 614 AGTGGGCAGCAATGACACCCACCCT 615 AGAACTCCAAGTTACATGGCCCCAC 616 AAACCTCAAGCTGTTCAGGTGCCGC ASGR2 206130_s_at 617 TGCAGGTGTACCGCTGGGTGTGTGA ggagaacgcacacctggtggtcatcaactcctgggaggagcagaaattcattg NM_001181.1 tacaacacacgaaccccttcaatacctggataggtctcacggacagtgatggc tcttggaaatgggtggatggcacagactataggcacaactacaagaactgggc tgtcactcagccagataattggcacgggcacgagctgggtggaagtgaagact gtgttgaagtccagccggatggccgctggaacgatgacttctgcctgcaggtg taccgctgggtgtgtgagaaaaggcggaatgccaccggcgaggtggcctgacc ccagcacacctctggctaacccataccccacacctgcccagctctggcttctc tgttgaggattttgaggaaaggaagaaacactgagacaggggtatggggaaga gctgagcaaagagagaaaggaggtagtttaagagtccctgaccctggaggact gagatcccacctccttctgtaattcattgtaattattataatcgtcagcctcttcaa 618 ATGCCACCGGCGAGGTGGCCTGACC 619 GGTAGTTTAAGAGTCCCTGACCCTG 620 CCCTGGAGGACTGAGATCCCACCTC 621 TTATTATAATCGTCAGCCTCTTCAA 622 GGAGAACGCACACCTGGTGGTCATC 623 TCATTGTACAACACACGAACCCCTT 624 GAACCCCTTCAATACCTGGATAGGT 625 TAATTGGCACGGGCACGAGCTGGGT 626 TGTTGAAGTCCAGCCGGATGGCCGC 627 GGCCGCTGGAACGATGACTTCTGCC MATK 206267_s_at 628 GCCGAGCGGAAGGGGCTAGACTCAA gccgagcggaaggggctagactcaagccggctgcccgtcaagtggacggcgcc NM_002378.1 cgaggctctcaaacacgggttcaccagcaagtcggatgtctggagttttgggg tgctgctctgggaggtcttctcatatggacgggctccgtaccctaaaatgtca ctgaaagaggtgtcggaggccgtggagaaggggtaccgcatggaaccccccga gggctgtccaggccccgtgcacgtcctcatgagcagctgctgggaggcagagc cgcccgccggccacccttccgcaaactggccgagaagctggcccgggagctac gcagtgcaggtgccccagcctccgtctcagggcaggacgccgacggtccacct cgccccgaagccaggagccctgaccccacccggtggcccttggccccagaggaccgag agagtggagagtgcggcgtgggggcac 629 GAAGGGGCTAGACTCAAGCCGGCTG 630 GTTCACCAGCAAGTCGGATGTCTGG 631 GCAAGTCGGATGTCTGGAGTTTTGG 632 CTCTGGGAGGTCTTCTCATATGGAC 633 TCTTCTCATATGGACGGGCTCCGTA 634 GCTCCGTACCCTAAAATGTCACTGA 635 CTGAAAGAGGTGTCGGAGGCCGTGG 636 AGGCCGTGGAGAAGGGGTACCGCAT 637 CCGTCTCAGGGCAGGACGCCGACGG 638 AGTGGAGAGTGCGGCGTGGGGGCAC ASGR1 206743_s_at 639 CTACCGCTGGGTCTGCGAGACAGAG aggagcagaaatttgtccagcaccacataggccctgtgaacacctggatgggc NM_001671.1 ctccacgaccaaaacgggccctggaagtgggtggacgggacggactacgagac gggcttcaagaactggaggccggagcagccggacgactggtacggccacgggc tcggaggaggcgaggactgtgcccacttcaccgacgacggccgctggaacgac gacgtctgccagaggccctaccgctgggtctgcgagacagagctggacaaggc cagccaggagccacctctcctttaatttatttcttcaatgcctcgacctgccg caggggtccgggattgggaatccgcccatctggggcctcttctgctttctcgg gaattttcatctaggattttaagggaaggggaaggatagggtgatgttccgaaggtga ggagcttgaaacccgtggcg 640 GGGTCTGCGAGACAGAGCTGGACAA 641 TGCCGCAGGGGTCCGGGATTGGGAA 642 TCTTCTGCTTTCTCGGGAATTTTCA 643 CTCGGGAATTTTCATCTAGGATTTT 644 GATAGGGTGATGTTCCGAAGGTGAG 645 GGTGAGGAGCTTGAAACCCGTGGCG 646 AGGAGCAGAAATTTGTCCAGCACCA 647 GAAATTTGTCCAGCACCACATAGGC 648 CCACATAGGCCCTGTGAACACCTGG 649 GAGCAGCCGGACGACTGGTACGGCC TXK 206828_at 650 TAGCCCCAGGAACCCTTGAGGTTCT tagccccaggaacccttgaggttcttcttcacaaggctgagagtgcttccttc NM_003328.1 ttgaagacgagtgtcattcatcacttcagtgatccatgcatagaatatgaaaa taaattcttccaactcatgggataaaggggactcccttgaagaatttcatgtt tttgggctgtatagctctttacagaaaatgcacctttataaatcacatgaatg ttagtattctggaaatgtcttttgttaatataatcttcccatgttatttaaca aattgtttttgcacatatctgattatattgaaagcagtttttttgcattcgag ttttaaacactgttataaaatgtagccaaagctcacctttgaacagatcccgg tgacattctatttccaggaaaatccggaacctgattttagttctgtgatttta cactttttacatgtgagattggacagtttcagaggccttattttgtcatactaagtg tctcctgtaatt 651 TTGAGGTTCTTCTTCACAAGGCTGA 652 GACGAGTGTCATTCATCACTTCAGT 653 TCACTTCAGTGATCCATGCATAGAA 654 GGGACTCCCTTGAAGAATTTCATGT 655 GTTTTTGGGCTGTATAGCTCTTTAC 656 AGCTCACCTTTGAACAGATCCCGGT 657 TCCCGGTGACATTCTATTTCCAGGA 658 GAGATTGGACAGTTTCAGAGGCCTT 659 TCAGAGGCCTTATTTTGTCATACTA 660 GTCATACTAAGTGTCTCCTGTAATT KIR3DL2 207314_x_at 661 GGAACTTCCAAATGCTGAGCCCAGA ggaacttccaaatgctgagcccagatccaaagttgtctcctgcccacgagcac NM_006737.1 cacagtcaggtcttgagggggttttctagggagacaacagccctgtctcaaaa ccaggttgccagatccaatgaaccagcagctggaatctgaaggcatcagtctg catcttaggggatcgctcttcctcacaccacgaatctgaacatgcctctctct tgcttacaaatgcctaaggtcgccactgcctgctgcagagaaaacacactcct ttgcttagcccacaaggtatctatttcacttgacccctgcccacctctccaac ctaactggcttacttcctagtcctacttgaggctgcaatcacactgaggaact cacaattccaaacatacaagaggctccctcttaacacggcacttacacacttg ctgttccaccttccctcatgctgttccacctcccctcagactatctttcagcc ttctgtcatcagtaaaatttataaattttttttataacttcagtgtagctctctcct 662 AGCCCAGATCCAAAGTTGTCTCCTG 663 CCACGAGCACCACAGTCAGGTCTTG 664 CAGTCTGCATCTTAGGGGATCGCTC 665 ACACCACGAATCTGAACATGCCTCT 666 AAGGTATCTATTTCACTTGACCCCT 667 TCTCCAACCTAACTGGCTTACTTCC 668 CTTCCTAGTCCTACTTGAGGCTGCA 669 AACACGGCACTTACACACTTGCTGT 670 TATCTTTCAGCCTTCTGTCATCAGT 671 TATAACTTCAGTGTAGCTCTCTCCT SH2D2A 207351_s_at 672 CACCCTGTCCTACGGAAGAGCTGGT caccctgtcctacggaagagctggtccaggcctgtcccaggaggccagaatac NM_003975.1 aggtggctcccagctgcattctgagaactctgtgattgggcaaggccctcccc tgccccaccagcccccacccgcctggagacacaccctcccccacaatctttct agacaggtgcttcaggacagaggacaggcatggcttccccttgggcctcctca gtaggcggtctggcctgacccccaacaaagaagcctggaggtcagagaagcaa atgcggagcctgctccctcctaagaagatcccaagaatccaatggctcagtcc ttggtgatctaagacagcaaagaagtgtgcaaggagggccctgttagctccca ctgtcctggtttctcctcctggagtctaatttccttggccctctgagcctttt gagtctgggccctggtccaatgctgctgttgtctgaggaatggtttggtgaga acagatgttagaacttgtttgttgattcttgtctggctaat 673 CTCCCAGCTGCATTCTGAGAACTCT 674 GAACTCTGTGATTGGGCAAGGCCCT 675 TCCCCCACAATCTTTCTAGACAGGT 676 AAGCAAATGCGGAGCCTGCTCCCTC 677 CTCCCTCCTAAGAAGATCCCAAGAA 678 CAATGGCTCAGTCCTTGGTGATCTA 679 GTGCAAGGAGGGCCCTGTTAGCTCC 680 TCCTGGAGTCTAATTTCCTTGGCCC 681 CTCTGAGCCTTTTGAGTCTGGGCCC 682 GTTTGTTGATTCTTGTCTGGCTAAT CD160 207840_at 683 AACAGAACAGCTTTCACCAAAGTGG tcagtgtaatccttgactttgctcctcaccatcagggcaaacttgccttcttc NM_007053.1 cctcctaagctccagtaaataaacagaacagctttcaccaaagtgggtagtat agtcctcaaatatcggataaatatatgcgtttttgtaccccagaaaaactttt cctccctcttcatcaacatagtaaaataagtcaaacaaaatgagaacaccaaa ttttgggggaataaatttttatttaacactgcaaaggaaagagagagaaaaca agcaaagataggtaggacagaaaggaagacagccagatccagtgattgacttg gcatgaaaatgagaaaatgcagacagacctcaacattcaacattcaacaacat ccatacagcactgctggaggaagaggaagatttgtgcagaccaagagcaccac agactacaactgcccagcttcatctaaatacttgttaacctctttggtcat 684 GTGGGTAGTATAGTCCTCAAATATC 685 ATATATGCGTTTTTGTACCCCAGAA 686 GACAGCCAGATCCAGTGATTGACTT 687 CAACAACATCCATACAGCACTGCTG 688 AAGAGCACCACAGACTACAACTGCC 689 TACAACTGCCCAGCTTCATCTAAAT 690 GCCCAGCTTCATCTAAATACTTGTT 691 AATACTTGTTAACCTCTTTGGTCAT 692 TCAGTGTAATCCTTGACTTTGCTCC 693 TTCCCTCCTAAGCTCCAGTAAATAA CEACAM3 208052_x_at 694 ATACCAAGAAAATGCCCCAGGCCTT ataccaagaaaatgccccaggccttcctgtgggggccgtcgccggcatcgtga NM_001815.1 ccggggtcctggtcggagtggcgctggtggccgcgctggtgtgtttcctgctc cttgccaaaactggaaggccgtggtccctcccacagctctgccttctcgatgt cccctctctccactgcctaggcccccctacccaaccccaggacagcagcttcc atctatgagaagtggcttcttagcttcctccaggagctgctcctgtgggttga tggagagtccccaaggcccccagccctggggatggggaaggacatgaagcctg agccagagaaccagctataagtcctgagaagacactggtgtctggggacaggg agggatggggtccctgatgaatatctggagacctcgacagcctgccctaggcc ctgggtgggtcaggacaaaggcctctcatcaccgcagaaagcgggggcttgcagggaa agtgaatgggcctgtggcccacctg 695 TTCCTGCTCCTTGCCAAAACTGGAA 696 CCAGGACAGCAGCTTCCATCTATGA 697 TTCTTAGCTTCCTCCAGGAGCTGCT 698 GGGTTGATGGAGAGTCCCCAAGGCC 699 GAAGCCTGAGCCAGAGAACCAGCTA 700 GGATGGGGTCCCTGATGAATATCTG 701 AATATCTGGAGACCTCGACAGCCTG 702 GGGTGGGTCAGGACAAAGGCCTCTC 703 GCCTCTCATCACCGCAGAAAGCGGG 704 AGTGAATGGGCCTGTGGCCCACCTG ZBP1 208087_s_at 705 GGGTTCAGGCCAGGTCTTTTGATGG gggttcaggccaggtcttttgatggccaggagtagatgacagggagttgcctt NM_030776.1 ggggaacctttggtgtgccaagaggaggtgggtagatgggagtggggctcggt cccccaggcccaggggactctctccactctttcctgggctcggggcatctgcc tggagttaccttccatcatggctacctgctgtggtttgaatgtttgagtccca acaaaattcatatcaaaacataatcccaactgggtgcagtggctcacgcctgt aatcccagcactttgggaggccgaggcgggcggatcaataggtcaggaaatccagac cgtcct 706 CCAGGTCTTTTGATGGCCAGGAGTA 707 GGCCAGGAGTAGATGACAGGGAGTT 708 TGCCTTGGGGAACCTTTGGTGTGCC 709 TGGGGAACCTTTGGTGTGCCAAGAG 710 GGTAGATGGGAGTGGGGCTCGGTCC 711 TAGATGGGAGTGGGGCTCGGTCCCC 712 GTGGTTTGAATGTTTGAGTCCCAAC 713 GAGTCCCAACAAAATTCATATCAAA 714 ACATAATCCCAACTGGGTGCAGTGG 715 TAGGTCAGGAAATCCAGACCGTCCT APLP2 208248_x_at 716 CCCTTCCAACTATGTCCAGATGTGC cccttccaactatgtccagatgtgcaggctcctcctctctggactttctccaa NM_001642.1 aggcactgaccctcggcctctactttgtcccctcacctccaccccctcctgtc accggccttgtgacattcactcagagaagaccacaccaaggaggggccgcggc tggcccaggagagaacacggggaggtttgtttgtgtgaaaggaaagtagtcca ggctgtccctgaaactgagtctgtggacactgtggaaagctttgaacaattgt gttttcgtcacaggagtctttgtaatgcttgtacagttgatgtcgatgctcac tgcttctgctttttctttctttttattttaaaaaatctgaaggttctggtaac ctgtggtgtatttttattttcctgtgactgtttttgttttgtttttttccttt ttcctcccctttagccctattcatgtctctacccactatgcacagattaaacttcac ctacaaactcct 717 TCCTCTCTGGACTTTCTCCAAAGGC 718 CCGGCCTTGTGACATTCACTCAGAG 719 AGAAGACCACACCAAGGAGGGGCCG 720 AGGAAAGTAGTCCAGGCTGTCCCTG 721 GCTGTCCCTGAAACTGAGTCTGTGG 722 GTGTTTTCGTCACAGGAGTCTTTGT 723 CAGTTGATGTCGATGCTCACTGCTT 724 GGTGTATTTTTATTTTCCTGTGACT 725 TCTCTACCCACTATGCACAGATTAA 726 GATTAAACTTCACCTACAAACTCCT CS 208660_at 727 AGAATACAAGCCACTACCTTCTGAC agaatacaagccactaccttctgacctccccaccccccaccaacccccatctt BC000105.1 ttaatatgctgtggggcatagaactccggaatgaccagcatgatattttcaga gtcttgtccccggggtattagcacctctttttgaacagggaattgattcaaga ttggacatggtctcctctgattatcaggtactggggctgagggcattaaaaat agtaagcctccctcctcgtcccctgcctcaagaaattgcctccttatttatca acatctttttcctccctttccctgagagctcacagtacaatgtttcagaagcc ccatttgcacaggttttcagcaactcagaatgctctacttctttttctttgag aaaggattaagatacactcctgctgtgcccccatctttcctccaaactcctgc ctgtgtttgtgtggatacccagtcccagaaccacactgttgagttggacacactgtaa acccct 728 TGCTGTGGGGCATAGAACTCCGGAA 729 TGATATTTTCAGAGTCTTGTCCCCG 730 TCTTGTCCCCGGGGTATTAGCACCT 731 GGTATTAGCACCTCTTTTTGAACAG 732 TGGACATGGTCTCCTCTGATTATCA 733 TGCCTCCTTATTTATCAACATCTTT 734 GCCCCATTTGCACAGGTTTTCAGCA 735 GCAACTCAGAATGCTCTACTTCTTT 736 TTGTGTGGATACCCAGTCCCAGAAC 737 TGAGTTGGACACACTGTAAACCCCT LTA4H 208771_s_at 738 GATTGGAATGCCTGGCTCTACTCTC gattggaatgcctggctctactctcctggactgcctcccataaagcccaatta J02959.1 tgatatgactctgacaaatgcttgtattgccttaagtcaaagatggattactg ccaaagaagatgatttaaattcattcaatgccacagacctgaaggatctctct tctcatcaattgaatgagtttttagcacagacgctccagagggcacctcttcc attggggcacataaagcgaatgcaagaggtgtacaacttcaatgccattaaca attctgaaatacgattcagatggctgcggctctgcattcaatccaagtgggag gacgcaattcctttggcgctaaagatggcaactgaacaaggaagaatgaagtt tacccggcccttattcaaggatcttgctgcctttgacaaatcccatgatcaag ctgtccgaacctaccaagagcacaaagcaagcatgcatcccgtgactgcaatgctggt gg 739 GCCACAGACCTGAAGGATCTCTCTT 740 GGATCTCTCTTCTCATCAATTGAAT 741 GAGTTTTTAGCACAGACGCTCCAGA 742 TGGGAGGACGCAATTCCTTTGGCGC 743 GGCCCTTATTCAAGGATCTTGCTGC 744 TTGCTGCCTTTGACAAATCCCATGA 745 AAATCCCATGATCAAGCTGTCCGAA 746 GTCCGAACCTACCAAGAGCACAAAG 747 CAAAGCAAGCATGCATCCCGTGACT 748 CATCCCGTGACTGCAATGCTGGTGG ANXA2P2 208816_x_at 749 CAGAAAGCGCTGCTGTACCTGTGTG tgccccacctccagaaagtatttgataggtacaagagttacagcccttatgac M62898.1 atgttggaaagcatcaggaaagaggttaaaggagacctggaaaatgctttcct gaacctggtccagcgcattcagaacaagcccttgtattttgctgatcagctgt acgactccatgaagggcaaggggacgcgagataaggtcctgatcagaatcatg gtctcccgcagtgaagtggacatgttgaaaattaggtctgaattcaagagaaa gtacggcaagtccctgtactactatatccagcaagacactaagggcgactacc agaaagcgctgctgtacctgtgtggtggagctgactgaagcccgacacagcct gagcgtccagaaatggtgctcaccatgcttccagctaacaggtctactaaaca tacaaaagtttagccgggcgtggtggcgctcgcctgtagtcccagctagtccggagc tgag 750 TGGTGGAGCTGACTGAAGCCCGACA 751 GACACAGCCTGAGCGTCCAGAAATG 752 CTCACCATGCTTCCAGCTAACAGGT 753 TAGTCCCAGCTAGTCCGGAGCTGAG 754 TGCCCCACCTCCAGAAAGTATTTGA 755 CTGAACCTGGTCCAGCGCATTCAGA 756 AAGCCCTTGTATTTTGCTGATCAGC 757 CTGATCAGCTGTACGACTCCATGAA 758 CTGATCAGAATCATGGTCTCCCGCA 759 GGCAAGTCCCTGTACTACTATATCC PLXNB2 208890_s_at 760 CGCCCAGCGTCTAGACTGTAGCATC cgcccagcgtctagactgtagcatcttcctctgagcaataccgccgggcaccg BC004542.1 caccagcaccagccccagccccagctccctccggccgcagaaccagcatcggg tgttcactgtcgagtctcgagtgatttgaaaatgtgccttacgctgccacgct gggggcagctggcctccgcctccgcccacgcaccagcagccgcctccatgccc taggttgggcccctgggggatctgagggcctgtggcccccagggcaagttccc agatcctatgtctgtctgtccaccacgagatgggaggaggagaaaaagcggta cgatgccttcctgacctcaccggcctccccaagggtgccggcactctgggtgg actcacggctgctgggccccacgtcaaaggtcaagtgagacgtaggtcaagtc ctacgtcggggcccagacatcctggggtcctggtctgtcagacaggctgccct agagccccacccagtccggggggactgggagcagttccaagaccaccc 761 GAACCAGCATCGGGTGTTCACTGTC 762 GTGTTCACTGTCGAGTCTCGAGTGA 763 TACGCTGCCACGCTGGGGGCAGCTG 764 CCAGGGCAAGTTCCCAGATCCTATG 765 TCCCAGATCCTATGTCTGTCTGTCC 766 AGAAAAAGCGGTACGATGCCTTCCT 767 GGCCCCACGTCAAAGGTCAAGTGAG 768 TCTGTCAGACAGGCTGCCCTAGAGC 769 TCCGGGGGGACTGGGAGCAGTTCCA 770 ACTGGGAGCAGTTCCAAGACCACCC CYFIP1 208923_at 771 GCACTCCGTAACTCAACATGGCATG gcactccgtaactcaacatggcatgcctttctctccgtaaactatttagtgag BC005097.1 atttttagggactatttttcagtatctctgtacctgttaaagggggtgctttt cgatctaaaaacttaattttataaaattgacttatttttctagactaaaattg tatatgcttttggtaattaggaactcttgagaatattggctgctgattgttgc catcacgttcctacaaaattgtttttctatgggatgttctggcagctgtgtca taaaatgctgctgggttcattcattcattccataagaaacttaataccagcaa atgcattaaatcccttgccagttaccattaactataactatttagcttttgtt tagggatctttctgatggtcttttatgagcaatcttagttctaagtcattgtt cccatcccttttttgtgtgtttcagaaaatagtgaacttgattcccctgcttccacta aatccagttgtga 772 GCCTTTCTCTCCGTAAACTATTTAG 773 TTTTCAGTATCTCTGTACCTGTTAA 774 GAGAATATTGGCTGCTGATTGTTGC 775 TTGTTGCCATCACGTTCCTACAAAA 776 TGGGATGTTCTGGCAGCTGTGTCAT 777 ATGCTGCTGGGTTCATTCATTCATT 778 GTTTAGGGATCTTTCTGATGGTCTT 779 CTTAGTTCTAAGTCATTGTTCCCAT 780 AATAGTGAACTTGATTCCCCTGCTT 781 CTGCTTCCACTAAATCCAGTTGTGA MAGED1 209014_at 782 GGACTGCACAGTTCATGGAGGCTGC ggactgcacagttcatggaggctgcagatgaggccttggatgctctggatgct AF217963.1 gctgcagctgaggccgaagcccgggctgaagcaagaacccgcatgggaattgg agatgaggctgtgtctgggccctggagctgggatgacattgagtttgagctgc tgacctgggatgaggaaggagattttggagatccctggtccagaattccattt accttctgggccagataccaccagaatgcccgctccagattccctcagacctt tgccggtcccattattggtcctggtggtacagccagtgccaacttcgctgcca actttggtgccattggtttcttctgggttgagtgagatgttggatattgctat caatcgcagtagtctttcccctgtgtgagctgaagcctcagattccttctaaa cacagctatctagagagccacatcctgttgactgaaagtggcatgcaagataa atttatttgctgttccttgtctactgctttttttccccttgtgtgctgtcaagt 783 ATGAGGCCTTGGATGCTCTGGATGC 784 TGGAGATCCCTGGTCCAGAATTCCA 785 TTCCATTTACCTTCTGGGCCAGATA 786 GGTCCCATTATTGGTCCTGGTGGTA 787 CCAACTTCGCTGCCAACTTTGGTGC 788 GTGCCATTGGTTTCTTCTGGGTTGA 789 TCCCCTGTGTGAGCTGAAGCCTCAG 790 CTATCTAGAGAGCCACATCCTGTTG 791 ATTTATTTGCTGTTCCTTGTCTACT 792 TTTTTCCCCTTGTGTGCTGTCAAGT SYNE1 209447_at 793 GAGGACCTTGATCTTGGCGAAAGCC gaggaccttgatcttggcgaaagccatcggtgtggcagctttagccctcctcc AF043290.1 agatcacatgtgtgcaaattatggcttcagagggtggaagataaacagtgacg ggggaacaaacagacaacaagaaggtttggaagaaatctggtttgagactctg aaccttagcactaaggagattgagtaaggacctccaaagttccccggactcat gaattctgggcccttggcattcgtgtgcacagccaaggacttcagtagaccat ctgggcagctttcccatggtgctgctccaaccatcagataaatgaccctcccc aagcaccatgtcagtgtcgtacaatctaccaaccaaccagtgctgaagagatt ttagaaccttgtaacatacaatttttaagagcttatatggcagcttcctttt 794 GCCATCGGTGTGGCAGCTTTAGCCC 795 TTGAGACTCTGAACCTTAGCACTAA 796 AAAGTTCCCCGGACTCATGAATTCT 797 CCCTTGGCATTCGTGTGCACAGCCA 798 GCACAGCCAAGGACTTCAGTAGACC 799 TCAGTAGACCATCTGGGCAGCTTTC 800 AACCATCAGATAAATGACCCTCCCC 801 GCACCATGTCAGTGTCGTACAATCT 802 GTGTCGTACAATCTACCAACCAACC 803 AGAGCTTATATGGCAGCTTCCTTTT CBLB 209682_at 804 GGAGACCGATGCTTGCTCAGGATGT ggagaccgatgcttgctcaggatgtcgacagctgtggcttccttgtttttgct U26710.1 agccatatttttaaatcagggttgaactgacaaaaataatttaaagacgttta cttcccttgaactttgaacctgtgaaatgctttaccttgtttacaatttggca aagttgcagtttgttcttgtttttagtttagttttgttttggtgttttgatac ctgtactgtgttcttcacagaccctttgtagcgtggtcaggtctgctgtaaca tttcccaccaactctcttgctgtccacatcaacagctaaatcatttattcata tggatctctaccatccccatgccttgcccaggtccagttccatttctctcatt cacaagatgctttgaaggttctgattttcaactgatcaaactaatgcaaaaaa aaaaagtatgtattcttcactactgagtttcttctttggaaaccatcactatt 805 CCTTGTTTTTGCTAGCCATATTTTT 806 GAACCTGTGAAATGCTTTACCTTGT 807 GGCAAAGTTGCAGTTTGTTCTTGTT 808 GTACTGTGTTCTTCACAGACCCTTT 809 CTTCACAGACCCTTTGTAGCGTGGT 810 GTAGCGTGGTCAGGTCTGCTGTAAC 811 GTTCCATTTCTCTCATTCACAAGAT 812 GAAGGTTCTGATTTTCAACTGATCA 813 TTCTTCACTACTGAGTTTCTTCTTT 814 TTCTTCTTTGGAAACCATCACTATT CD247 210031_at 815 ACTGTACTGGGCCATGTTGTGCCTC aagcgcagatgctagcacatgccctaatgtctgtatcactctgtgtctgagtg J04132.1 gcttcactcctgctgtaaatttggcttctgttgtcaccttcacctcctttcaa ggtaactgtactgggccatgttgtgcctccctggtgagagggccgggcagagg ggcagatggaaaggagcctaggccaggtgcaaccagggagctgcaggggcatg ggaaggtgggcgggcaggggagggtcagccagggcctgcgagggcagcgggag cctccctgcctcaggcctctgtgccgcaccattgaactgtaccatgtgctaca ggggccagaagatgaacagactgaccttgatgagctgtgcacaaagtggcata aaaaacagtgtggttacacagtgtgaataaagtgctgcggagcaagaggaggc cgttgattcacttcacgctttcagcgaatgacaaaatcatctttgtgaaggcctcgca ggaagacgcaacacatgggacctat 816 AAAGGAGCCTAGGCCAGGTGCAACC 817 TGCCGCACCATTGAACTGTACCATG 818 GACTGACCTTGATGAGCTGTGCACA 819 TGATTCACTTCACGCTTTCAGCGAA 820 ATCATCTTTGTGAAGGCCTCGCAGG 821 GGAAGACGCAACACATGGGACCTAT 822 AAGCGCAGATGCTAGCACATGCCCT 823 AATGTCTGTATCACTCTGTGTCTGA 824 GGCTTCACTCCTGCTGTAAATTTGG 825 AAATTTGGCTTCTGTTGTCACCTTC PRKCQ 210038_at 826 AATCCATTCATCCTGATTGGGCATG aatccattcatcctgattgggcatgaaatccatggtcaagaggacaagtggaa AL137145 agtgagagggaaggtttgctagacaccttcgcttgttatcttgtcaagataga aaagatagtatcatttcacccttgccagtaaaaacctttccatccacccattc tcagcagactccagtattggcacagtcactcactgccattctcacactataac aagaaaagaaatgaagtgcataagtctcctgggaaaagaaccttaaccccttc tcgtgccatgactggtgatttcatgactcataagcccctccgtaggcatcattcaaga tcaatggcccatgcatgctgtttgcagca 827 GACACCTTCGCTTGTTATCTTGTCA 828 ATCATTTCACCCTTGCCAGTAAAAA 829 CCATTCTCAGCAGACTCCAGTATTG 830 CCAGTATTGGCACAGTCACTCACTG 831 ACTGCCATTCTCACACTATAACAAG 832 GAAGTGCATAAGTCTCCTGGGAAAA 833 CCTTCTCGTGCCATGACTGGTGATT 834 TGATTTCATGACTCATAAGCCCCTC 835 CCCCTCCGTAGGCATCATTCAAGAT 836 TGGCCCATGCATGCTGTTTGCAGCA FYN 210105_s_at 837 GGCCCGGGTCTGCGGAGAGAGGCCT ggcccgggtctgcggagagaggccttgtcccagaggctgccccacccctcccc M14333.1 attagctttcaattccgtagccagctgctccccagcagcggaaccgcccagga tcagattgcatgtgactctgaagctgacgaacttccatggccctcattaatga cacttgtccccaaatccgaacctcctctgtgaagcattcgagacagaaccttg ttatttctcagactttggaaaatgcattgtatcgatgttatgtaaaaggccaa acctctgttcagtgtaaatagttactccagtgccaacaatcctagtgctttcc ttttttaaaaatgcaaatcctatgtgattttaactctgtcttcacctgattca actaaaaaaaaaaagtattattttccaaaagtggcctctttgtctaa 838 AGCTTTCAATTCCGTAGCCAGCTGC 839 AACCGCCCAGGATCAGATTGCATGT 840 GATTGCATGTGACTCTGAAGCTGAC 841 CTTCCATGGCCCTCATTAATGACAC 842 TAATGACACTTGTCCCCAAATCCGA 843 GACAGAACCTTGTTATTTCTCAGAC 844 AAAGGCCAAACCTCTGTTCAGTGTA 845 TCCAGTGCCAACAATCCTAGTGCTT 846 CCTATGTGATTTTAACTCTGTCTTC 847 TTCCAAAAGTGGCCTCTTTGTCTAA LILRB4 210152_at 848 AGGACGGGGTGGAAATGGACACTCG ccaacactggcgtcagggaaaacacaggacattggcccagagacaggctgatt U82979.1 tccaacgtcctccaggggctgccgagccagagcccaaggacgggggcctacag aggaggtccagcccagctgctgacgtccagggagaaaacttctgtgctgccgt gaagaacacacagcctgaggacggggtggaaatggacactcggagcccacacg atgaagacccccaggcagtgacgtatgccaaggtgaaacactccagacctagg agagaaatggcctctcctccctccccactgtctggggaattcctggacacaaa ggacagacaggcagaagaggacagacagatggacactgaggctgctgcatctg aagccccccaggatgtgacctacgcccagctgcacagctttaccctcagacagaagg caactg 849 CACAGCTTTACCCTCAGACAGAAGG 850 TTTACCCTCAGACAGAAGGCAACTG 851 CCAACACTGGCGTCAGGGAAAACAC 852 GGAAAACACAGGACATTGGCCCAGA 853 ATTGGCCCAGAGACAGGCTGATTTC 854 GAGACAGGCTGATTTCCAACGTCCT 855 GAGCCCAAGGACGGGGGCCTACAGA 856 GCTGACGTCCAGGGAGAAAACTTCT 857 AAACTTCTGTGCTGCCGTGAAGAAC 858 TCTGTGCTGCCGTGAAGAACACACA GZMB 210164_at 859 GCCAAGCGGACCAGAGCTGTGCAGC gccaagcggaccagagctgtgcagcccctcaggctacctagcaacaaggccca J03189.1 ggtgaagccagggcagacatgcagtgtggccggctgggggcagacggcccccc tgggaaaacattcacacacactacaagaggtgaagatgacagtgcaggaagat cgaaagtgcgaatctgacttacgccattattacgacagtaccattgagttgtg cgtgggggacccagagattaaaaagacttcctttaagggggactctggaggcc ctcttgtgtgtaacaaggtggcccagggcattgtctcctatggacgaaacaat ggcatgcctccacgagcctgcaccaaagtctcaagctttgtacactggataaa gaaaaccatgaaacgctactaactacaggaagcaaactaagcccccgctgtaatgaa acaccttctctggagcca 860 TGCGAATCTGACTTACGCCATTATT 861 GACTTACGCCATTATTACGACAGTA 862 ACGACAGTACCATTGAGTTGTGCGT 863 TTGAGTTGTGCGTGGGGGACCCAGA 864 ACTCTGGAGGCCCTCTTGTGTGTAA 865 GCATTGTCTCCTATGGACGAAACAA 866 AAGTCTCAAGCTTTGTACACTGGAT 867 TACAGGAAGCAAACTAAGCCCCCGC 868 CTAAGCCCCCGCTGTAATGAAACAC 869 TAATGAAACACCTTCTCTGGAGCCA ANXA2 210427_x_at 870 CTGATCAGAATCATGGTCTCCCGCA gaaaatgctttcctgaacctggttcagtgcattcagaacaagcccctgtattt BC001388.1 tgctgatcggctgtatgactccatgaagggcaaggggacgcgagataaggtcc tgatcagaatcatggtctcccgcagtgaagtggacatgttgaaaattaggtct gaattcaagagaaagtacggcaagtccctgtactattatatccagcaagacac taagggcgactaccagaaagcgctgctgtacctgtgtggtggagatgactgaa gcccgacacggcctgagcgtccagaaatggtgctcaccatgcttccagctaac aggtctagaaaaccagcttgcgaataacagtccccgtggccatccctgtgagg gtgacgttagcattacccccaacctcattttagttgcctaagcattgcctggc cttcctgtctagtctctcctgtaagccaaagaaatgaacattccaaggagttg gaagtgaagtctatgatgtgaaacactttgcctcctgtgtactgtgtcataaa 871 CAGAAAGCGCTGCTGTACCTGTGTG 872 CTCACCATGCTTCCAGCTAACAGGT 873 ACCAGCTTGCGAATAACAGTCCCCG 874 CGTGGCCATCCCTGTGAGGGTGACG 875 GAGGGTGACGTTAGCATTACCCCCA 876 AGTTGCCTAAGCATTGCCTGGCCTT 877 TGCCTCCTGTGTACTGTGTCATAAA 878 GAAAATGCTTTCCTGAACCTGGTTC 879 CAAGCCCCTGTATTTTGCTGATCGG 880 GCTGATCGGCTGTATGACTCCATGA NFATC3 210555_s_at 881 TCTGCACCTTCATCCTTAATATGTC tctgcaccttcatccttaatatgtcacagtttgtgtgatccagcgtcatttcc U85430.1 acctgatggggcaactgtgagcattaaacctgaaccagaagatcgagagccta actttgcaaccattggtctgcaggacatcactttagat 882 CATCCTTAATATGTCACAGTTTGTG 883 ACAGTTTGTGTGATCCAGCGTCATT 884 TTGTGTGATCCAGCGTCATTTCCAC 885 GTCATTTCCACCTGATGGGGCAACT 886 GGGGCAACTGTGAGCATTAAACCTG 887 ACCTGAACCAGAAGATCGAGAGCCT 888 GATCGAGAGCCTAACTTTGCAACCA 889 GAGCCTAACTTTGCAACCATTGGTC 890 CAACCATTGGTCTGCAGGACATCAC 891 TGGTCTGCAGGACATCACTTTAGAT KLRD1 210606_x_at 892 GAAAGACTCTGACTGCTGTTCTTGC gaaagactctgactgctgttcttgccaagaaaaatgggttgggtaccggtgca U30610.1 actgttacttcatttccagtgaacagaaaacttggaacgaaagtcggcatctc tgtgcttctcagaaatccagcctgcttcagcttcaaaacacagatgaactgga ttttatgagctccagtcaacaattttactggattggactctcttacagtgagg agcacaccgcctggttgtgggagaatggctctgcactctcccagtatctattt ccatcatttgaaacttttaatacaaagaactgcatagcgtataatccaaatgg aaatgctttagatgaatcctgtgaagataaaaatcgttatatctgtaagcaac agctcatttaaatgtttcttggggcagagaaggtggagagtaaagacccaaca ttactaacaatgatacagttgcatgttatattattactaattgtctacttctggagt cta 893 GTACCGGTGCAACTGTTACTTCATT 894 ACGAAAGTCGGCATCTCTGTGCTTC 895 CTGTGCTTCTCAGAAATCCAGCCTG 896 CAGCCTGCTTCAGCTTCAAAACACA 897 TTTTACTGGATTGGACTCTCTTACA 898 CTTACAGTGAGGAGCACACCGCCTG 899 GCACACCGCCTGGTTGTGGGAGAAT 900 GTGGGAGAATGGCTCTGCACTCTCC 901 TCCCAGTATCTATTTCCATCATTTG 902 ACTAATTGTCTACTTCTGGAGTCTA PMS2L11 210707_x_at 903 GAAGTCAGTCCATCAGATTTGCTCT ctggaccctatcgtacagaacctgctaaggccatcaaacctattgatcggaag U38980.1 tcagtccatcagatttgctctgggccagtggtactgagtctaagcactgcagt gaaggagttagtagaaaacagtctggatgctggtgccactaatattgatctaa agcttaaggactatggaatggatctcattgaagtttcaggcaatggatgtggg gtagaagaagaaaacttcgaaggcttaatgatgtcaccatttctacctgccac gtctcggcgaaggttgggactcgactggtgtttgatcacgatgggaaaatcat ccagaagaccccctacccccaccccagagggaccacagtcagcgtgaagcagt tattttctacgctacctgtgcgccataaggaatttcaaaggaatattaagaagaaac atgctgcttccccttc 904 GCTCTGGGCCAGTGGTACTGAGTCT 905 AACAGTCTGGATGCTGGTGCCACTA 906 TAATGATGTCACCATTTCTACCTGC 907 GCCACGTCTCGGCGAAGGTTGGGAC 908 GTTGGGACTCGACTGGTGTTTGATC 909 GAGGGACCACAGTCAGCGTGAAGCA 910 CTACGCTACCTGTGCGCCATAAGGA 911 AGAAGAAACATGCTGCTTCCCCTTC 912 CTGGACCCTATCGTACAGAACCTGC 913 GAACCTGCTAAGGCCATCAAACCTA HOP 211597_s_at 914 AAGCTATGTGTATCTTCTGTGTAAA aagctatgtgtatcttctgtgtaaagcagtggcttcactggaaaaatggtgtg AB059408.1 gctagcatttccctttgagtcatgatgacagatggtgtgaaaaccatctaagt ttgcttttgaccatcacctcccagtagcaatttgctttcataatccatttagc aatccaggcctctgttgaaaagataatatgagggagaagggaacacatttcct tctgaacttacttccctaagtcactttccttatgtatcatctaatacaatgat ggttgagtgaaaatacagaaggggtgtttgagtattcagatttcataaaacac ttccttggaatatagctgcattaacttggaaagaagcctgttgggccagaagacaga 915 AATGGTGTGGCTAGCATTTCCCTTT 916 TAAGTTTGCTTTTGACCATCACCTC 917 TCACCTCCCAGTAGCAATTTGCTTT 918 TAATCCATTTAGCAATCCAGGCCTC 919 GCAATCCAGGCCTCTGTTGAAAAGA 920 GAAGGGAACACATTTCCTTCTGAAC 921 CTTCCCTAAGTCACTTTCCTTATGT 922 AGTCACTTTCCTTATGTATCATCTA 923 ACTTCCTTGGAATATAGCTGCATTA 924 GAAGCCTGTTGGGCCAGAAGACAGA NCALD 211685_s_at 925 TGGGTGAGGAGACCTAGCATGCCCT tgggtgaggagacctagcatgccctattggcagtgctcaggagctgcatccca AF251061.1 cttttccctgctctgaatcgaagtcctagttccttcctttgattctcctttgg taggtggaatcagttaatgttttgagaaacctgcctgggctctgcccttagtc atgacatctcgctgagccagacccactctgttccttggaacctagagctggag tgaggagtagaggtctccggctattccagaaagaaaagtgagccacatgcagg ctgatgaatgccgacacttccagaatgtatagaaatagtccctgtcctggcct gccactgaccctgtctgtattttctcggaggttgtttttctccttctccttcc caggaaggtctttgtatgtcgaatccagtgcactcaagtttggccaagggact ccacagcacccagaagactgcatgcctcaaggtttatgtcactcctctgctgggctg ttcattgtcattgc 926 AGCATGCCCTATTGGCAGTGCTCAG 927 TCCCTGCTCTGAATCGAAGTCCTAG 928 TTAGTCATGACATCTCGCTGAGCCA 929 GGAGTAGAGGTCTCCGGCTATTCCA 930 GAATGCCGACACTTCCAGAATGTAT 931 ACCCTGTCTGTATTTTCTCGGAGGT 932 TCTCGGAGGTTGTTTTTCTCCTTCT 933 GTATGTCGAATCCAGTGCACTCAAG 934 GCCTCAAGGTTTATGTCACTCCTCT 935 CTGCTGGGCTGTTCATTGTCATTGC LOC130074 212017_at 936 GGATGAGCGGCGTCTGTGTAGGGAC ggatgagcggcgtctgtgtagggacccccccccgggcctgcagaagggtggtg BF677404 tgctcccaggactggcatgacaggtgtctcctcctcaccacaggctgtgccca tgngtccctgtgcagaccagtgggcaaggcagctgggccagatctcaggccag ccgtttgtgctcctagcagggttgctgtgctggccacacggagaggccctaga gagcctcatggattgtaactaaagaagaaacggttcctttttgntttttttaa aaatgatttttaaataccgttttttacaccgttctctcggtactttttttaag ctaagtcagcattgtcttccagtgttaaaggcatccctcacctctgcattgaa cttacgtatccatgccaaggaatggaatttccatcctgagccagttcagttaggtgt caatt 937 TGCAGAAGGGTGGTGTGCTCCCAGG 938 GGACTGGCATGACAGGTGTCTCCTC 939 TCCCTGTGCAGACCAGTGGGCAAGG 940 TGTGCTCCTAGCAGGGTTGCTGTGC 941 CACACGGAGAGGCCCTAGAGAGCCT 942 GAGAGCCTCATGGATTGTAACTAAA 943 CCAGTGTTAAAGGCATCCCTCACCT 944 CTCACCTCTGCATTGAACTTACGTA 945 GAACTTACGTATCCATGCCAAGGAA 946 GAGCCAGTTCAGTTAGGTGTCAATT GPR56 212070_at 947 TCCAAGGACTGAGACTGACCTCCTC tccaaggactgagactgacctcctctggtgacactggcctagngcctgacact AL554008 ctcctaagaggttctctccaagcccccaaatagctccaggcgccctcggccgc ccatcatggttaattctgtccaacaaacacacacgggtagattgctggcctgt tgtaggtggtagggacacagatgaccgacctggtcactcctcctgccaacatt cagtctggtatgtgaggcgtgcgtgaagcaagaactcctggagctacagggac agggagccatcattcctgcctgggaatcctggaagacttcctgcaggagtcag cgttcaatcttgaccttgaagatgggaaggatgttctttttacgtaccaattct 948 ACACTCTCCTAAGAGGTTCTCTCCA 949 GGCCGCCCATCATGGTTAATTCTGT 950 CACACGGGTAGATTGCTGGCCTGTT 951 TAGGGACACAGATGACCGACCTGGT 952 CAGTCTGGTATGTGAGGCGTGCGTG 953 AGGCGTGCGTGAAGCAAGAACTCCT 954 AGGGACAGGGAGCCATCATTCCTGC 955 ACTTCCTGCAGGAGTCAGCGTTCAA 956 GTCAGCGTTCAATCTTGACCTTGAA 957 GATGTTCTTTTTACGTACCAATTCT SPTBN1 212071_s_at 958 AAACCATTTGTATCTGGCATCACTT aaaccatttgtatctggcatcacttactaacacacgacatgcggcttttctgc BE968833 atcaactgctatgacggttaagaatgtcagtatacaagaaggaatagaaaact gatactgttttaaataatctgtaatttcaatttttttttttttttngctgaaa tacattatattgtacgtttgagataattctagntacaaagtataataaaacta gatngtataataaaccctttaaatcattggtaagtgtacaagtggtggnaact gaagcatttactggnacaaagtaatgttnactctaatggttacttgctcgtgc gttgnnccacactgtgttataatttgcttcatttccttgctatttgatacata gtgtgcatttctctgtcactgtaactattgtaatgacaaattttcatcttact gcacaatcaaaatgacattgataggaatgaactccagaggctgggcctgaaca gggaggtggtcgctcaggcctggtgctcagtcgtacgacctgtacct 959 TCTGGCATCACTTACTAACACACGA 960 TAACACACGACATGCGGCTTTTCTG 961 ACATGCGGCTTTTCTGCATCAACTG 962 TCTAATGGTTACTTGCTCGTGCGTT 963 TAATTTGCTTCATTTCCTTGCTATT 964 TGCATTTCTCTGTCACTGTAACTAT 965 AATTTTCATCTTACTGCACAATCAA 966 TAGGAATGAACTCCAGAGGCTGGGC 967 GAGGCTGGGCCTGAACAGGGAGGTG 968 GTGCTCAGTCGTACGACCTGTACCT ATP2B4 212135_s_at 969 GTGGAAAAGCCTCTAAATGCATCCC gtggaaaagcctctaaatgcatcccttcctttctttcctgcttcctttgcctt AW517686 acaattgaagcagcccgtggtaccatcacagtatgcagagacttcctcacctt tcatatctagggaccacccccgatgcattggtgagggtgggcacttataaatg cctgctattgttaagccattccagcctcttcctctgaatagaccagacgccctttca cttagttcagtgcca 970 TGCTTCCTTTGCCTTACAATTGAAG 971 CAATTGAAGCAGCCCGTGGTACCAT 972 CAGTATGCAGAGACTTCCTCACCTT 973 CACCTTTCATATCTAGGGACCACCC 974 ACCACCCCCGATGCATTGGTGAGGG 975 GGTGGGCACTTATAAATGCCTGCTA 976 GCCTGCTATTGTTAAGCCATTCCAG 977 CAGCCTCTTCCTCTGAATAGACCAG 978 TCTGAATAGACCAGACGCCCTTTCA 979 CGCCCTTTCACTTAGTTCAGTGCCA GTF3C2 212429_s_at 980 GTATCTGCATGAAGGCTCCTGTCTG gtatctgcatgaaggctcctgtctgactattccaggatccaatattactgcct AW194657 tctgaaacttcctctttagggtaaccatcatgtatgcccacgagggtgatagt aattcgtgagactgaagttgcttagagtacttctttgaccaaggaataccaca gacaccctaccgatagaacagtggctcagatcttacttgctcctgcttacgaa gtattcccaatcactggtcatctgaccctacttgaacactcctgaacagtcat gttttttaaaatcttcctttatatcaagtcagagagtatacttctataaattt cactcatggatgttaggaaatctagtcatcttccctgtgattgccctgttaagtattt aaccatagctatcatgtgtttccca 981 GGCTCCTGTCTGACTATTCCAGGAT 982 TATTACTGCCTTCTGAAACTTCCTC 983 TAACCATCATGTATGCCCACGAGGG 984 CAAGGAATACCACAGACACCCTACC 985 CCCTACCGATAGAACAGTGGCTCAG 986 TGCTCCTGCTTACGAAGTATTCCCA 987 TTCCCAATCACTGGTCATCTGACCC 988 GGAAATCTAGTCATCTTCCCTGTGA 989 TCCCTGTGATTGCCCTGTTAAGTAT 990 AACCATAGCTATCATGTGTTTCCCA AUTS2 212599_at 991 TCAGACACACACAGGTCGCCAGTGA tcagacacacacaggtcgccagtgacttcacacacacctcatgtgagaaccat AK025298.1 gccttttttagtgtgtcctatttcatacctgtacacacttcctcgttttgtaa tgagatttacttacacccaaacagatcctgaaagaaagcttcaagttttctca gatgatggatatgttttcactgtattcaataactgacggatgtaaggtgcacg tttcctgatgnntgacgcactgtattccagctggtgatcaagtctgggaacag ccgtaacaggtcaaccttgtggagccatcgcgagttagagggtgaaagatggc agaaaaaaaagtcttgtgtgtgagtgtgttttttgagtttgcatcaatcttaatgtct cttcataatacttttataatacattaagcctcttgtctacat 992 TAGTGTGTCCTATTTCATACCTGTA 993 TGTACACACTTCCTCGTTTTGTAAT 994 TACTTACACCCAAACAGATCCTGAA 995 GGATGTAAGGTGCACGTTTCCTGAT 996 GACGCACTGTATTCCAGCTGGTGAT 997 GGTGATCAAGTCTGGGAACAGCCGT 998 GAACAGCCGTAACAGGTCAACCTTG 999 CAACCTTGTGGAGCCATCGCGAGTT 1000 GCATCAATCTTAATGTCTCTTCATA 1001 AATACATTAAGCCTCTTGTCTACAT STX10 212625_at 1002 AGCTGGAGAGTAGAGGGTCCCGCCT ccaggttctgaagcacatgtccggccgcgttggagaagagctggacgagcagg NM_003765.1 gcatcatgctggatgccttcgcccaagagatggaccacacccagtcccgcatg gacggggtcctcaggaagttggccaaagtatcccacatgacgagtgaccgccg acagtggtgtgccatcgccgtgctagtgggggtgcttctcctcgttctcatct tactattctctctctgaccccagccctccctggcaggctggtcccttaagcct ggggagccaccaagcactttggagctggcctcgccccctaggaggagagggtc cctcctgggtagctggagagtagagggtcccgcctggggagctgtccccatgg ctctcccctagagccagtgggacccttcaggaccctgggctggaaccaccacc actggtcctgtctcaagtgcacttagggggtggtggaggcagggacacctgagacac acctgtctccat 1003 TGGTCCTGTCTCAAGTGCACTTAGG 1004 ACACCTGAGACACACCTGTCTCCAT 1005 CCAGGTTCTGAAGCACATGTCCGGC 1006 CCGGCCGCGTTGGAGAAGAGCTGGA 1007 GGCATCATGCTGGATGCCTTCGCCC 1008 TGCCTTCGCCCAAGAGATGGACCAC 1009 TCCCGCATGGACGGGGTCCTCAGGA 1010 GTATCCCACATGACGAGTGACCGCC 1011 TGGTCCCTTAAGCCTGGGGAGCCAC 1012 GGAGCCACCAAGCACTTTGGAGCTG WWP1 212638_s_at 1013 GGATCTACCACCATATAAGAGTTAT ggatctaccaccatataagagttatgaacaactaaaggaaaaacttctttttg BF131791 caatagaagagacagagggattnggacaagaatgaatgtggcttcttatttng gaggagctcttgcatttaaataccccagccaagaaaaattgcacagatagtgt atataagctgttcattctgtacagtgaattttccgaacctctcaaagtatgtt ttccgttcttccacagaaatatgcaaaacagttcatccttttctactttattt attgttcccttgaaatgactgaccaggaaaaagatcatccttaaattttgaag caagtgagagactttattaaaaatacatatatatctatataaacatatatgat agtggctctagttttatagagctccaagtgtattaaacatgacagccattcattcata aagatctggatttgctttaccttgttaa 1014 GGAGCTCTTGCATTTAAATACCCCA 1015 TGCATTTAAATACCCCAGCCAAGAA 1016 AAGCTGTTCATTCTGTACAGTGAAT 1017 TACAGTGAATTTTCCGAACCTCTCA 1018 GAACCTCTCAAAGTATGTTTTCCGT 1019 ATGTTTTCCGTTCTTCCACAGAAAT 1020 GCAAAACAGTTCATCCTTTTCTACT 1021 ATTGTTCCCTTGAAATGACTGACCA 1022 TATGATAGTGGCTCTAGTTTTATAG 1023 ATCTGGATTTGCTTTACCTTGTTAA RFTN1 212646_at 1024 TGCTGTTCATCCCACATCGTGTGGG tgctgttcatcccacatcgtgtggggcagtgtccatcccctgcagctacttgg D42043.1 tgacttaacaactccaggagccctgtcagctgccctcctccanctaaanccct tcgactcttctgctttgacaaagaaaatgacattgggganggggaggtgctcc gcctcccagcttttctcaaaatagtcctatagatactggtaatctggaaatga agaagtaattctgtctctgcacctacttttgcagaatgttcaaggaagtattc tgtgttagtattaatgccaaaaagttgtttttaaaggttttgtactcagcaca tcatacaaaccacattacttctgtcacttcagggcatcgggactggctggcgc ccttgttatgtgctattttaatcagtgtaacattggtcaagttgttacccatg tatgctgtgtttatcatgtgtatatcgtccagaaagtattaaggctttaggta gatgcaactggcgaaccttggagagggaatgctgattgtcttgaccaaacccaca 1025 CCTGCAGCTACTTGGTGACTTAACA 1026 TAACAACTCCAGGAGCCCTGTCAGC 1027 GTCTCTGCACCTACTTTTGCAGAAT 1028 TACAAACCACATTACTTCTGTCACT 1029 CTGTCACTTCAGGGCATCGGGACTG 1030 GCGCCCTTGTTATGTGCTATTTTAA 1031 GTTACCCATGTATGCTGTGTTTATC 1032 GTTTATCATGTGTATATCGTCCAGA 1033 GATGCAACTGGCGAACCTTGGAGAG 1034 GCTGATTGTCTTGACCAAACCCACA IL1RN 212657_s_at 1035 GGTACTATGTTAGCCCCATAATTTT ggtactatgttagccccataattttttttttccttttaaaacacttccataat AW083357 ctggactcctctgtccaggcactgctgcccagcctccaagctccatctccact ccagattttttacagctgcctgcagtactttacctcctatcagaagtttctca gctcccaaggctctgagcaaatgtggctcctgggggttctttcttcctctgct gaaggaataaattgctccttgacattgtagagcttctggcacttggagacttg tatgaaagatggctgtgcctctgcctgtctcccccaccnggctgggagctctg cagagcaggaaacatgactcgtatatgtctcaggtccctgcagggccaagcac ctagcctcgctcttggcaggtactcagcgaatgaatgctgtatatgttgggtgcaaag ttccctacttcctgtgacttcagctctgtttta 1036 ACACTTCCATAATCTGGACTCCTCT 1037 GATTTTTTACAGCTGCCTGCAGTAC 1038 CAGTACTTTACCTCCTATCAGAAGT 1039 AGCTCCCAAGGCTCTGAGCAAATGT 1040 GAGCAAATGTGGCTCCTGGGGGTTC 1041 ATAAATTGCTCCTTGACATTGTAGA 1042 TGACTCGTATATGTCTCAGGTCCCT 1043 CTCTTGGCAGGTACTCAGCGAATGA 1044 TGTTGGGTGCAAAGTTCCCTACTTC 1045 TTCCTGTGACTTCAGCTCTGTTTTA ZNF364 212742_at 1046 TGAGGACTCTACTCGGCAAAGCCAG ttaccttgcaatcacttctttcacagcagttgtattgtgccgtggctagaact AL530462 gcatgacacatgtcctgtatgtaggaagagcttaaatggtgaggactctactc ggcaaagccagagcactgaggcctctgcaagcaacagatttagcaatgacagt cagctacatgaccgatggactttctgaagctaaagaccacacctgaatcaggg ctgtggtaatcatcttaccatagctgtaaattgtatcaaaacaaaaaattagt agatggatttaggaatatgtaagaaactcaacacataatataaatgcaatgaa tgtttttcttctttaaatttaaagttagtatctacagatggaattgtatctac aaccaaatgcctcttatccctgaattcagagtgataattttataagtgtgaaa cttaattatgtagggctccccccgtctgaatagaattaattccttaaagtcta gttagggtcctgctgtctgtcatgttgccttgtaacggatgtttccacctccttctcc aacctctaccccaccattagtgtatttt 1047 CACTGAGGCCTCTGCAAGCAACAGA 1048 CATGACCGATGGACTTTCTGAAGCT 1049 GAATCAGGGCTGTGGTAATCATCTT 1050 ATCTACAACCAAATGCCTCTTATCC 1051 TCTAGTTAGGGTCCTGCTGTCTGTC 1052 CTGTCTGTCATGTTGCCTTGTAACG 1053 CTCTACCCCACCATTAGTGTATTTT 1054 TTACCTTGCAATCACTTCTTTCACA 1055 ACAGCAGTTGTATTGTGCCGTGGCT 1056 GTGCCGTGGCTAGAACTGCATGACA PPP1R16B 212750_at 1057 TAACTTGGGGATGGTCTCCCCTGCC taacttggggatggtctcccctgccccagggcacataagagcaaaggctccaa AB020630.1 tggtcagtggatgactctgcaaaagtgaccccctgtgccagaagctatagccc tctccccaacaggtctctcttgttggccagagggcctgcttcccatgggcatt gcaagtgccaccgtgcggggcctggctctgcacacccaggaaaagtctgcaga cccccagccctccgcaataattcaccagaccagaagccactggtgtacagaga acacttaaaaaaatgtattttatgtgaaaaaaaattaaaactctgtatactgt atcagcagctttgtgtaaaaatggcaatcaagagagtctaatatatttaaaac ttttttaaaaaaaatcttcgcagatctttgatatcgtactgaggtaacttcca cgtagccccttgccacgcggcaccggtgggccttgggtccaaaactgtggctc agccacatcccaaagggggcacatgtccctggagttgcttccagctgccaaggcctgt gacagaattcgctgtt 1058 CTGCCCCAGGGCACATAAGAGCAAA 1059 GGATGACTCTGCAAAAGTGACCCCC 1060 CTCCCCAACAGGTCTCTCTTGTTGG 1061 CCTGCTTCCCATGGGCATTGCAAGT 1062 ATGGGCATTGCAAGTGCCACCGTGC 1063 CTCCGCAATAATTCACCAGACCAGA 1064 GTATACTGTATCAGCAGCTTTGTGT 1065 AAAATCTTCGCAGATCTTTGATATC 1066 TACTGAGGTAACTTCCACGTAGCCC 1067 AAGGCCTGTGACAGAATTCGCTGTT NCAM1 212843_at 1068 GAATGTGAGAGCCTGGGTGTCTGAG gaatgtgagagcctgggtgtctgagaccgggagggcccagcagtgaggggcag AA126505 gctcttctggtcaccaggctgttcagtggactcagttcttcatcttgtaatgt cgatggctttgccacaccaggccaagcccatgccataccttgtcaagactgtc aaagtggttgtggttaggtcaaactggttttggttctgatggttaggaagaaa caggtcagccctcagatcacctggcccgggacagctgaccccctagaaccctg gctctgccattagctaggacctaagactctgcccacattttggtctgttctctcccat tacacataggtttgtctcagcatgcaagagt 1069 GCCTGGGTGTCTGAGACCGGGAGGG 1070 CTCTTCTGGTCACCAGGCTGTTCAG 1071 GGCTGTTCAGTGGACTCAGTTCTTC 1072 GGACTCAGTTCTTCATCTTGTAATG 1073 CTTGTAATGTCGATGGCTTTGCCAC 1074 CATGCCATACCTTGTCAAGACTGTC 1075 GAAGAAACAGGTCAGCCCTCAGATC 1076 GCTCTGCCATTAGCTAGGACCTAAG 1077 TTAGCTAGGACCTAAGACTCTGCCC 1078 TAGGTTTGTCTCAGCATGCAAGAGT NKG7 213915_at 1079 ATTTCTGGTTTGAGGCTGTGGGTCC atttctggtttgaggctgtgggtcccacccactcagctcactcgggcctctgg NM_005601.1 ccaacagggcatggngacatcatatcaggctacatccacgtgacgcagacctt cagcattatggctgttctgtgggccctggtgtccgtgagcttcctggtcctgt cctgcttcccctcactgttccccccaggccacggcccgcttgtctcaaccacc gcagcctttgctgcagccatctccatggtggtggccatggcggtgtacaccag cgagcggtgggaccagcctccacacccccagatccagaccttcttctcctggt ccttctacctgggctgggtctcagctatcctcttgctctgtacaggtgccctg agcctgggtgctcactgtggcggtccccgtcctggctatgaaaccttgtgagcagaa ggcaagagcggcaagatgagttttgagcgttgtattcca 1080 GACATCATATCAGGCTACATCCACG 1081 TCATATCAGGCTACATCCACGTGAC 1082 ACGCAGACCTTCAGCATTATGGCTG 1083 CATTATGGCTGTTCTGTGGGCCCTG 1084 TGGCCATGGCGGTGTACACCAGCGA 1085 TACACCAGCGAGCGGTGGGACCAGC 1086 CTATCCTCTTGCTCTGTACAGGTGC 1087 CGTCCTGGCTATGAAACCTTGTGAG 1088 GTGAGCAGAAGGCAAGAGCGGCAAG 1089 GATGAGTTTTGAGCGTTGTATTCCA HLA-A 213932_x_at 1090 GAAGAACCCTGACTTTGTTTCTGCA gacagacctcaggagggctattggtccaggacccacacctgctttcttcatgt AI923492 /// HLA- ttcctgatcccgccctgggtctgcagtcacacatttctggaaacttctctggg H /// gtccaagactaggaggttcnnctnggaccttanggccntggntcntttctggt LOC642047 atctcacanggacattnncttctcacagatagaaaaggagggagttacactca /// ggctgcanncagtgacagtgcccaggctctgatgtgtcnctcacagcttgtaa LOC649853 agtgtgagacagctgccttgtgtgggactgagaggcaagagttgttcctgccc /// ttccctttgtgacttgaagaaccctgactttgtttctgcaaaggcacctgcat LOC649864 gtgtctgtgttcgtgtaggcntaatgtgaggaggtggggagaccaccccaccc cnatgtccaccatgaccctcttcccacgctgacctgtgctccctccccaatca tctttcctgttccagagaggtggggctgaggtgtctccatctctgtctcaacttcat ggtgcactgagctgtaacttcttc 1091 AAGGCACCTGCATGTGTCTGTGTTC 1092 CAATCATCTTTCCTGTTCCAGAGAG 1093 CATCTCTGTCTCAACTTCATGGTGC 1094 TGGTGCACTGAGCTGTAACTTCTTC 1095 GACAGACCTCAGGAGGGCTATTGGT 1096 GGCTATTGGTCCAGGACCCACACCT 1097 GGTCTGCAGTCACACATTTCTGGAA 1098 GGAAACTTCTCTGGGGTCCAAGACT 1099 AGACAGCTGCCTTGTGTGGGACTGA 1100 TGCCCTTCCCTTTGTGACTTGAAGA YPEL1 213996_at 1101 GCCGAACTGTCACCGAACGTACAGC gccgaactgtcaccgaacgtacagctgtatccactgcagagcacacctggcca NM_013313.1 atcatgacgagctcatctccaagtcctttcaggggagccagggacgcgcctac ctcttcaattccgtggtgaacgtgggctgcggccctgcagaggagagggtcct tctcaccgggctgcatgcggttgccgacatctactgcgagaactgcaagacca cgctcgggtggaaatacgagcatgcctttgagagcagtcagaaatataaggaa ggaaaattcatcattgagcttgctcatatgatcaaagacaatggctgggagta atgtgcgaactttcccttctccttngaatgctgttttgtgaaagaaactgtga atgtaatggaaacgtaggagcatctggtgacagcctttcttgccctctgacct caaaggctagctgcgcatagctcttgacactcncggccatctctgtgggtaaggtgt ccctcggatctgtcctcttcgtgtacacagttgtt 1102 CGTACAGCTGTATCCACTGCAGAGC 1103 ACACCTGGCCAATCATGACGAGCTC 1104 TCCAAGTCCTTTCAGGGGAGCCAGG 1105 TGCATGCGGTTGCCGACATCTACTG 1106 GAGTAATGTGCGAACTTTCCCTTCT 1107 TAGGAGCATCTGGTGACAGCCTTTC 1108 GCCCTCTGACCTCAAAGGCTAGCTG 1109 TAGCTGCGCATAGCTCTTGACACTC 1110 TGTGGGTAAGGTGTCCCTCGGATCT 1111 TGTCCTCTTCGTGTACACAGTTGTT ZAP70 214032_at 1112 AAGGGCCGGAGGTCATGGCCTTCAT aagggccggaggtcatggccttcatcgagcagggcaagcggatggantgccca AI817942 ccagagtgtnccacccgaactgtacgcactcatgagtgactgctggatctaca agtgggaggatcgccccgacttcctgaccgtggagcagcgcatgcgagcctgt tactacagcctggccagcaaggtggaagggcccccaggcagcacacagaaggc tgaggctgcctgtgcctgagctcccgctgcccaggggagccctccacnccggc tcttccccaccctcagccccaccccaggtcctgcagtctggctgagccctgct tggttgtctccacacacagctgggctgtggtagggggtgtctcaggccacacc ggccttgcattgcctgcctggccccctgtcctctctggctggggagcagggag gtccgggagggtgcggctgtgcagcctgtcctgggctggtggctcccggaggg ccctgagctgagggcattgcttacacggatgccttcccctgggccctgacatt ggagcctgggcatcctcaggtggtcaggcgtagatcaccagaataaacccagcttccc 1113 CCCGAACTGTACGCACTCATGAGTG 1114 TCATGAGTGACTGCTGGATCTACAA 1115 CATGCGAGCCTGTTACTACAGCCTG 1116 CACAGCTGGGCTGTGGTAGGGGGTG 1117 AGCAGGGAGGTCCGGGAGGGTGCGG 1118 GGCATTGCTTACACGGATGCCTTCC 1119 TGGGCCCTGACATTGGAGCCTGGGC 1120 TGACATTGGAGCCTGGGCATCCTCA 1121 GGTGGTCAGGCGTAGATCACCAGAA 1122 ATCACCAGAATAAACCCAGCTTCCC CTSW 214450_at 1123 GGAGAGAAGGGCTATTTCCGGCTGC caggacttcatcatgctgcagaacaacgagcacagaattgcgcagtacctggc NM_001335.1 cacttatggccccatcaccgtgaccatcaacatgaagccccttcagctatacc ggaaaggtgtgatcaaggccacacccaccacctgtgacccccagcttgtggac cactctgtcctgctggtgggttttggcagcgtcaagtcagaggaggggatatg ggcagagacagtctcatcgcagtctcagcctcagcctccacaccccaccccat actggatcctgaagaactcctggggggcccaatggggagagaagggctatttc cggctgcaccgagggagcaatacctgtggcatcaccaagttcccgctcactgcccgtg tgcagaaaccggatatgaagccccgagtctc 1124 CGGCTGCACCGAGGGAGCAATACCT 1125 ATACCTGTGGCATCACCAAGTTCCC 1126 CTCACTGCCCGTGTGCAGAAACCGG 1127 AACCGGATATGAAGCCCCGAGTCTC 1128 CAGGACTTCATCATGCTGCAGAACA 1129 GCGCAGTACCTGGCCACTTATGGCC 1130 AGCCCCTTCAGCTATACCGGAAAGG 1131 GGGTTTTGGCAGCGTCAAGTCAGAG 1132 GAGACAGTCTCATCGCAGTCTCAGC 1133 CCACCCCATACTGGATCCTGAAGAA PRF1 214617_at 1134 CCAACGCAAATTCGCAAACTTTCTT ccaacgcaaattcgcaaactttcttaaaacattatgagttncnntttgctatt AI445650 tttttttttttttttagctcatcggctatcgttagtgctagtggattttacat gtggcccnnnannnnnnnncnnncaacgtggcccagagaagccaaaagattgg atacgcatcagacagatggaaaagggagattcagactgtttttcagggaggtg gctgggtttacacgctaatcccgattcaccctgtccaaactgcctaagccctc cgccattntcaagccctgcagtcacagctacacagatcacagcttcagccagg agctgggcagaaggccaanaggctgttcccaccaggctgctcagggntggtct tttaggacccttcccttgagccctntatggtgtggcaaagccttcattgcctt aactggagccccatcagctccagctgctctgtnttntttgcccncaatgcttt gcccctgagacaaatggaggcctgtcctgacctgtctcaccatgtacatagctt 1135 GCTCATCGGCTATCGTTAGTGCTAG 1136 TGCTAGTGGATTTTACATGTGGCCC 1137 AGATTGGATACGCATCAGACAGATG 1138 GAGGTGGCTGGGTTTACACGCTAAT 1139 GGGTTTACACGCTAATCCCGATTCA 1140 GCAGTCACAGCTACACAGATCACAG 1141 GCCTTCATTGCCTTAACTGGAGCCC 1142 CAATGCTTTGCCCCTGAGACAAATG 1143 GACAAATGGAGGCCTGTCCTGACCT 1144 ACCTGTCTCACCATGTACATAGCTT SULT1A1 215299_x_at 1145 AAGATCCTGGAGTTTGTGGGGCGCT aagatcctggagtttgtggggcgctccctnccagaggagacngtggacntcat U37025 ggttnagcacacgtcgttcaaggagatgaagaagaaccctatgaccaactaca ccaccgtccnccnggagttcatggaccacagcatctcccccttcatgaggaaa ggcatggctggggacnngngnngnccacnttcaccgtggcgcagaatgagcgc ttcgatgcggacntatgcggagaagatggcaggncngcagcctcangcttccg ctntgagcngtgagaggggnnncntggagtcacngcagagggagtgtgcgaat caaacctgaccaagcggntcaagaataaaatatgaattgagggccngggacgg taggtcatgtctgtaatcccagcaatttggaggctgaggtgggaggatcattt gagcccaggagttcgagaccaacctgggcaacatagtgagattctgttaaaaa aataaaataaaataaaaccaatttttaaaaagagaataaaatatgattgtgggccagg cagagtggctcatgc 1146 AGCACACGTCGTTCAAGGAGATGAA 1147 AGAAGAACCCTATGACCAACTACAC 1148 GGAGTTCATGGACCACAGCATCTCC 1149 CATCTCCCCCTTCATGAGGAAAGGC 1150 TTCACCGTGGCGCAGAATGAGCGCT 1151 GCAGAATGAGCGCTTCGATGCGGAC 1152 GGGAGTGTGCGAATCAAACCTGACC 1153 GTGCGAATCAAACCTGACCAAGCGG 1154 GGACGGTAGGTCATGTCTGTAATCC 1155 GTGGGCCAGGCAGAGTGGCTCATGC C7ORF24 215380_s_at 1156 GAAAATGGTTTGCCGCTGGAGTATC gaaaatggtttgccgctggagtatcaagagaagttaaaagcaatagaaccaaa AK021779.1 tgactatacaggaaaggtctcagaagaaattgaagacatcatcaaaaaggggg aaacacaaactctttagaacataacagaatatatctaagggtattctatgtgc taatataaaatatttttaacacttgagaacagggatctgggggatctccacgt ttgatccattttcagcagtgctctgaaggagtatcttacttgggtgattcctt gtttttagactataaaaagaaactgggataggagttagacaatttaaaagggg tgtatgagggcctgaaatatgtgacaaatgaatgtgagtaccccttctatgaa cactgaaagctattctcttgaattgatcttaagtgtctccttgctctggtaaa agatagatttgtagctcacttgatgatggtgctggtgaattgctctgctctgtctgag att 1157 ATCTAAGGGTATTCTATGTGCTAAT 1158 ATCTGGGGGATCTCCACGTTTGATC 1159 CAGCAGTGCTCTGAAGGAGTATCTT 1160 GGAGTATCTTACTTGGGTGATTCCT 1161 GGGTGATTCCTTGTTTTTAGACTAT 1162 ACAAATGAATGTGAGTACCCCTTCT 1163 ATTGATCTTAAGTGTCTCCTTGCTC 1164 GTGTCTCCTTGCTCTGGTAAAAGAT 1165 AGATAGATTTGTAGCTCACTTGATG 1166 GAATTGCTCTGCTCTGTCTGAGATT HOMER3 215489_x_at 1167 CAATGTCCACAGCCAGGGAGCAGCC gagggacactcatagtccctcctctctccctaggggccaaaccagtgctcctg AI871287 ccacctctctggctgccccctagagcctgcccatcccagcctgaccaatgtcc acagccagggagcagccaatcttcagcacacgggcgcacgtgttccaaattga cccagccaccaagcgaaactggatcccagcgggcaagcacgcactcactgtct cctatttctacgatgccacccgcaatgtgtaccgcatcatcagcatcggaggc gccaaggccatcatcaacagcactgtcactcccaacatgaccttcaccaaaac ttcccagaagttcgggcagtgggccgacagtcgcgccaacacagtctatggcc tgggctttgcctctgaacagcatctgacacagtttgccgagaagttccaggaa gtgaaggaagcagccaggctggccagggagaaatctcaggatggctggggtgg gccccagtcggctctggttgttggcagctttggggctgtttttgagcttctcatt 1168 GGGCGCACGTGTTCCAAATTGACCC 1169 GTACCGCATCATCAGCATCGGAGGC 1170 GGCCATCATCAACAGCACTGTCACT 1171 AAGTTCGGGCAGTGGGCCGACAGTC 1172 AGTCGCGCCAACACAGTCTATGGCC 1173 GCTTTGCCTCTGAACAGCATCTGAC 1174 GACACAGTTTGCCGAGAAGTTCCAG 1175 CCCAGTCGGCTCTGGTTGTTGGCAG 1176 TGGGGCTGTTTTTGAGCTTCTCATT 1177 GAGGGACACTCATAGTCCCTCCTCT LILRA5 215838_at 1178 TCCTGCAGGTATGGTCAGAACCCAG tcctgcaggtatggtcagaacccagtgacctcctggagattccggtctcagga AF212842.1 gcagctgataacctcagtccgtcacanaacaagtctgactctgggactgcctc acaccttcaggattacgcagtagagaatctcatccgcatgggcatggccggct tgatcctggtggtccttgggattctgatatttcaggattggcacagccagaga agcccccaagctgcagctggaaggtgaacagaagagagaacaatgcaccattg aatgctggagccttggaagcgaatctgatggtcctaggaggttcgggaagaccatctg aggcctatgccatctggactgtctgctggcaatttcttt 1179 TGGAGATTCCGGTCTCAGGAGCAGC 1180 GAGCAGCTGATAACCTCAGTCCGTC 1181 TGCCTCACACCTTCAGGATTACGCA 1182 GGTCCTTGGGATTCTGATATTTCAG 1183 AATGCACCATTGAATGCTGGAGCCT 1184 GCTGGAGCCTTGGAAGCGAATCTGA 1185 GCGAATCTGATGGTCCTAGGAGGTT 1186 GGTTCGGGAAGACCATCTGAGGCCT 1187 TGAGGCCTATGCCATCTGGACTGTC 1188 TGGACTGTCTGCTGGCAATTTCTTT PTGDR 215894_at 1189 CGCGCGCGGACGGGAGGGAAGCGTC gccatgcgcaacctctatgcgatgcaccggcggctgcagcggcacccgcgctc U31099.1 ctgcaccagggactgtgccgagccgcgcgcggacgggagggaagcgtcccctc agcccctggaggagctggatcacctcctgctgctggcgctgatgaccgtgctc ttcactatgtgttctctgcccgtaatttatcgcgcttactatggagcatttaa ggatgtcaaggagaaaaacaggacctctgaagaagcagaagacctccgagcct tgcgatttctatctgtgatttcaattgtggacccttggatttttatcattttc agatctccagtatttcggatattttttcacaagattttcattagacctcttag gtacaggagccggtgcagcaattccactaacatggaatccagtctgtgacagtgttt ttcactc 1190 TGCCCGTAATTTATCGCGCTTACTA 1191 GAAGAAGCAGAAGACCTCCGAGCCT 1192 AGCCTTGCGATTTCTATCTGTGATT 1193 GCCATGCGCAACCTCTATGCGATGC 1194 GATTTCAATTGTGGACCCTTGGATT 1195 TTTTCAGATCTCCAGTATTTCGGAT 1196 TTTCACAAGATTTTCATTAGACCTC 1197 AGACCTCTTAGGTACAGGAGCCGGT 1198 AACATGGAATCCAGTCTGTGACAGT 1199 CAGTCTGTGACAGTGTTTTTCACTC LPXN 216250_s_at 1200 GCTTTCTGCCTGACACAGTTGTCGA gctttctgcctgacacagttgtcgaagggcattttcagggagcagaatgacaa X77598.1 gacctattgtcaaccttgcttcaataagctcttcccactgtaatgccaactga tccatagcctcttcagattccttataaaatttaaaccaagagaggagaggaaa gggtaaattttctgttactgaccttctgcttaatagtcttatagaaaaaggaa aggtgatgagcaaataaaggaacttctagactttacatgactaggctgataat cttattttttaggcttctatacagttaattctataaattctctttctccctct cttctccaatcaagcacttggagttagatctaggtccttctatctcgtccctc tacagatgtattttccacttgcataattcatgccaacactggttttcttaggt ttctccattttcacctctagtgatggccctactcatatcttctctaatttggt cctgatacttgtttcttttcacgttttcccatttccctgtggctcactgtcttacaa tcactg 1201 AAGACCTATTGTCAACCTTGCTTCA 1202 TCTTCCCACTGTAATGCCAACTGAT 1203 CCAACTGATCCATAGCCTCTTCAGA 1204 CTGTTACTGACCTTCTGCTTAATAG 1205 GTTAGATCTAGGTCCTTCTATCTCG 1206 TATCTCGTCCCTCTACAGATGTATT 1207 TTTCACCTCTAGTGATGGCCCTACT 1208 ACTCATATCTTCTCTAATTTGGTCC 1209 GGTCCTGATACTTGTTTCTTTTCAC 1210 GTGGCTCACTGTCTTACAATCACTG PYHIN1 216748_at 1211 CCACCCTCTGGATCCCAATATTGAG ccaccctctggatcccaatattgagatcttatcctcagggaatcctcacttag AK024890.1 acccctgtaacaggttaaatcttcatggtgttctgtttcctaggaacttcttt cttttctactgtttatgacaactgaagttaataagtgtttatctttcccacct actcaaagtagttccaagattagggctagtttgtaattctgtggaccactgta aacgagggcctagttcagtgtctgcctcatgggaagcttccaataaatacctttg 1212 TTATCCTCAGGGAATCCTCACTTAG 1213 CCTCACTTAGACCCCTGTAACAGGT 1214 AAATCTTCATGGTGTTCTGTTTCCT 1215 GTGTTCTGTTTCCTAGGAACTTCTT 1216 TAATAAGTGTTTATCTTTCCCACCT 1217 ATCTTTCCCACCTACTCAAAGTAGT 1218 GTAGTTCCAAGATTAGGGCTAGTTT 1219 GTGGACCACTGTAAACGAGGGCCTA 1220 CGAGGGCCTAGTTCAGTGTCTGCCT 1221 GGGAAGCTTCCAATAAATACCTTTG SLC35E2 217122_s_at 1222 GTCTCTGAAGTATTTCCTCCAGTTT gtctctgaagtatttcctccagtttccctgcgggcccctatgtttgagtttga AL031282 tggctgctggatcctcactcaacgaaaactcggttggaaactgttccgcctgg cagtccttttttgttgttttccatctcatttcccttccatctgaaagtggcat tcagctgacttgctcatttagactgttcacggagtctgaatctgccaacgtgg tgttggaggctccaccttgaaaagggccacagtcagggcaactttccccatac aggaaaacttgaaaattacatcaacagtctacgtcacagccaaattatatttc ctttataccaaacaaaactatggagaactaaaagtacatcacacaaaacgttt atagtgttttgcatgtgacctatttcagtatttatataactagattagtgctt tctagcaaacggttctgttaattagcgagtcactgttgattctgctgtggtggtaag ttgataccgtgtaactaatcccgtggat 1223 GGGCCCCTATGTTTGAGTTTGATGG 1224 GGATCCTCACTCAACGAAAACTCGG 1225 CTCGGTTGGAAACTGTTCCGCCTGG 1226 GACTTGCTCATTTAGACTGTTCACG 1227 GAGTCTGAATCTGCCAACGTGGTGT 1228 TCAGGGCAACTTTCCCCATACAGGA 1229 TACATCAACAGTCTACGTCACAGCC 1230 GTGCTTTCTAGCAAACGGTTCTGTT 1231 TAGCGAGTCACTGTTGATTCTGCTG 1232 ATACCGTGTAACTAATCCCGTGGAT TRA@ // 217143_s_at 1233 GTTGACCTGTCATAGCCTTGTTAAA gaaggtgaacatgatgtccctcacagtgcttgggctacgaatgctgtttgcaa X06557.1 TRD@ agactgttgccgtcaattttctcttgactgccaagttatttttcttgtaaggc tgactggcatgaggaagctacactcctgaagaaaccaaaggcttacaaaaatg catctccttggcttctgacttctttgtgattcaagttgacctgtcatagcctt gttaaaatggctgctagccaaaccactttttcttcaaagacaacaaacccagc tcatcctccagcttgatgggaagacaaaagtcctggggaaggggggtttatgtcctaa ctgctttgta 1234 TCAAAGACAACAAACCCAGCTCATC 1235 GCTCATCCTCCAGCTTGATGGGAAG 1236 GGGTTTATGTCCTAACTGCTTTGTA 1237 GAAGGTGAACATGATGTCCCTCACA 1238 GCTTGGGCTACGAATGCTGTTTGCA 1239 AGACTGTTGCCGTCAATTTTCTCTT 1240 AATTTTCTCTTGACTGCCAAGTTAT 1241 TTTTCTTGTAAGGCTGACTGGCATG 1242 GAAGCTACACTCCTGAAGAAACCAA 1243 AAAAATGCATCTCCTTGGCTTCTGA TRATRD 217147_s_at 1244 TCTCCTTTCTCACCAATGGGCAATA tctcctttctcaccaatgggcaatagcccataattgaaataaatttctgattg AJ240085.1 aaaggtataggaaacattaaaatgcattactaagagaagtaatataattttct tacaaagtatttttcccaaagatagctttactatttcaaaaattgtcaaatta atgcatgctccttacaacaaacaaatatcaaaaagagtttaggaattctacta gccagagatagtcacttggagaaactttctatatatccttctaaatatttttc tgggcatgctcatgtatgtacatcagttgtttctttttattttgaaccaaaaa tgtggtttcttttgtacacattacttaaactttctttccagtcaacaatatat tgtggatttattttcactgttatatttaactatatataaatacgcatatattgtaat tttaatgtctgcttagcaccccactgataaccaaatcacag 1245 TCCTTTCTCACCAATGGGCAATAGC 1246 TATTTTTCCCAAAGATAGCTTTACT 1247 GTCAAATTAATGCATGCTCCTTACA 1248 AATGCATGCTCCTTACAACAAACAA 1249 ATGCTCCTTACAACAAACAAATATC 1250 GAGTTTAGGAATTCTACTAGCCAGA 1251 ACTAGCCAGAGATAGTCACTTGGAG 1252 GATAGTCACTTGGAGAAACTTTCTA 1253 GAAACTTTCTATATATCCTTCTAAA 1254 CACCCCACTGATAACCAAATCACAG S100A6 217728_at 1255 GGGACCGCTATAAGGCCAGTCGGAC gggaccgctataaggccagtcggactgcgacatagcccatcccctcgaccgct NM_014624.2 cgcgtcgcatttggccgcctccctaccgctccaagcccagccctcagccatgg catgccccctggatcaggccattggcctcctcgtggccatcttccacaagtac tccggcagggagggtgacaagcacaccctgagcaagaaggagctgaaggagctgatc cagaaggagctcaccattggctcgaagctgcagg 1256 TCGTGGCCATCTTCCACAAGTACTC 1257 TTCCACAAGTACTCCGGCAGGGAGG 1258 CCGCTATAAGGCCAGTCGGACTGCG 1259 TCCGGCAGGGAGGGTGACAAGCACA 1260 GACAAGCACACCCTGAGCAAGAAGG 1261 GCTGATCCAGAAGGAGCTCACCATT 1262 GAAGGAGCTCACCATTGGCTCGAAG 1263 AGCTCACCATTGGCTCGAAGCTGCA 1264 CTCACCATTGGCTCGAAGCTGCAGG 1265 GCCAGTCGGACTGCGACATAGCCCA RAB31 217763_s_at 1266 AACATTGTAATGGCCATCGCTGGAA aacattgtaatggccatcgctggaaacaagtgcgacctctcagatattaggga NM_006868.1 ggttcccctgaaggatgctaaggaatacgctgaatccataggtgccatcgtgg ttgagacaagtgcaaaaaatgctattaatatcgaagagctctttcaaggaatc agccgccagatcccacccttggacccccatgaaaatggaaacaatggaacaat caaagttgagaagccaaccatgcaagccagccgccggtgctgttgacccaagg gcgtggtccacggtacttgaagaagccagagcccacatcctgtgcactgctga aggaccctacgctcggtggcctggcacctcactttgagaagagtgagcacact ggctttgcatcctggaaggcctgcagggggcggggcaggaaatgtacctgaaa aggattttagaaaaccctgggaaacccaccacaccaccacaaaatggcctttagtgt 1267 GAAACAAGTGCGACCTCTCAGATAT 1268 GGAGGTTCCCCTGAAGGATGCTAAG 1269 TACGCTGAATCCATAGGTGCCATCG 1270 GTGCCATCGTGGTTGAGACAAGTGC 1271 TTCAAGGAATCAGCCGCCAGATCCC 1272 TGAGAAGCCAACCATGCAAGCCAGC 1273 CGTGGTCCACGGTACTTGAAGAAGC 1274 ATCCTGTGCACTGCTGAAGGACCCT 1275 GAGTGAGCACACTGGCTTTGCATCC 1276 ACCACCACAAAATGGCCTTTAGTGT EVL 217838_s_at 1277 GATCATCGACGCCATCAGGCAGGAG gatcatcgacgccatcaggcaggagctgagtgggatcagcaccacgtaagggg NM_016337.1 ccggcctcgctgcgctgattcgtcgagcccatccggcgacagaggacagccag aagcccagccagccccagactccagtgcaccagagcacgcacaggagcctggg cgcgctgctgtgaaacgtcctgacctgtgatcacacatgacagtgaggaaacc aagtgcaactcctgggtttttttagattctgcctgacacggaacaccaggtct gctcgtcttttttgtgttttatatttgcttatttaaggtacatttctttgggtttcta gagacgcccctaagtcacctgcttcattagacggtttccaggttttct 1278 TGGGATCAGCACCACGTAAGGGGCC 1279 CCCATCCGGCGACAGAGGACAGCCA 1280 GTGCACCAGAGCACGCACAGGAGCC 1281 TGAAACGTCCTGACCTGTGATCACA 1282 GGAAACCAAGTGCAACTCCTGGGTT 1283 TCCTGGGTTTTTTTAGATTCTGCCT 1284 TAGATTCTGCCTGACACGGAACACC 1285 CTGACACGGAACACCAGGTCTGCTC 1286 GGTACATTTCTTTGGGTTTCTAGAG 1287 TCATTAGACGGTTTCCAGGTTTTCT SMAD3 218284_at 1288 GGTGTAGTGGCTTTTTGGCTCAGCA ggtgtagtggctttttggctcagcatccagaaacaccaaaccaggctggctaa NM_015400.1 acaagtggccgcgtgtaaaaacagacagctctgagtcaaatctgggcccttcc acaagggtcctctgaaccaagccccactcccttgctaggggtgaaagcattac agagagatggagccatctatccaagaagccttcactcaccttcactgctgctg ttgcaactcggctgttctggactctgatgtgtgtggagggatggggaatagaa cattgactgtgttgattaccttcactattcggccagcctgaccttttaataac tttgtaaaaagcatgtatgtatttatagtgttttagatttttctaacttttat atcttaaaagcagagcacctgtttaagcattgtacccctattgttaaagatttgtgt cctctcattccctctcttcctcttgtaagtgcccttctaata 1289 GGCTCAGCATCCAGAAACACCAAAC 1290 GGCTGGCTAAACAAGTGGCCGCGTG 1291 CAGCTCTGAGTCAAATCTGGGCCCT 1292 CCCACTCCCTTGCTAGGGGTGAAAG 1293 GAGCCATCTATCCAAGAAGCCTTCA 1294 CTGTTCTGGACTCTGATGTGTGTGG 1295 GCCAGCCTGACCTTTTAATAACTTT 1296 GCACCTGTTTAAGCATTGTACCCCT 1297 GTTAAAGATTTGTGTCCTCTCATTC 1298 TCCTCTTGTAAGTGCCCTTCTAATA MAPBPIP 218291_at 1299 AGCCAAGCCAACACTGGAGGCGTCC gagaggcacctcggagatctgggtgcaaaagcccagggttaggaaccgtagca NM_014017.1 tgctgcgccccaaggctttgacccaggtgctaagccaagccaacactggaggc gtccagagcaccctgctgctgaataacgagggatcactgctggcctactctgg ttacggggacactgacgcccgggtcaccgctgccatagccagtaacatctggg ccgcctacgaccggaacgggaaccaagcgtttaatgaagacaatctcaaattc atcctcatggactgcatggagggccgtgtagccatcacccgagtggccaacct tctgctgtgtatgtatgccaaggagaccgtgggctttggaatgctcaaggcca aggcccaggctttggtgcagtacctggaggagcccctcacccaagtggcggcatctt aacggcattg 1300 ATAACGAGGGATCACTGCTGGCCTA 1301 CTACTCTGGTTACGGGGACACTGAC 1302 TAGCCAGTAACATCTGGGCCGCCTA 1303 AATCTCAAATTCATCCTCATGGACT 1304 TGGACTGCATGGAGGGCCGTGTAGC 1305 GAGAGGCACCTCGGAGATCTGGGTG 1306 GACCGTGGGCTTTGGAATGCTCAAG 1307 AAGTGGCGGCATCTTAACGGCATTG 1308 GGTTAGGAACCGTAGCATGCTGCGC 1309 CCAAGGCTTTGACCCAGGTGCTAAG PGLS 218388_at 1310 CCTACAGGAGCGGGAGAAGATTGTG cctacaggagcgggagaagattgtggctcccatcagtgactccccgaagccac NM_012088.1 cgccacagcgtgtgaccctcacactacctgtcctgaatgcagcacgaactgtc atctttgtggcaactggagaaggcaaggcagctgttctgaagcgcattttgga ggaccaggaggaaaacccgctgcccgccgccctggtccagccccacaccgggaaact gtgctggttcttggacgag 1311 GAAGATTGTGGCTCCCATCAGTGAC 1312 CTCACACTACCTGTCCTGAATGCAG 1313 ACCTGTCCTGAATGCAGCACGAACT 1314 CAGCACGAACTGTCATCTTTGTGGC 1315 GTGGCAACTGGAGAAGGCAAGGCAG 1316 GGCAAGGCAGCTGTTCTGAAGCGCA 1317 GGCAGCTGTTCTGAAGCGCATTTTG 1318 AAGCGCATTTTGGAGGACCAGGAGG 1319 CCCCACACCGGGAAACTGTGCTGGT 1320 GAAACTGTGCTGGTTCTTGGACGAG SPON2 218638_s_at 1321 CTGCCCCGAGCTCGAAGAAGAGGCT ctgccccgagctcgaagaagaggctgagtgcgtccctgataactgcgtctaag NM_012445.1 accagagccccgcagcccctggggcccccggagccatggggtgtcgggggctc ctgtgcaggctcatgctgcaggcggccgaggcacagggggtttcgcgctgctc ctgaccgcggtgaggccgcgccgaccatctctgcactgaagggccctctggtg gccggcacgggcattgggaaacagcctcctcctttcccaaccttgcttcttag gggcccccgtgtcccgtctgctctcagcctcctcctcctgcaggataaagtca tccccaaggctccagctactctaaattatggtctccttataagttattgctgc tccaggagattgtccttcatcgtccaggggcctggctcccacgtggttgcaga tacctcagacctggtgctctaggctgtgctgagcccactctcccgagggcgca tccaagcgggggccacttgagaagtgaataaatggggcggtttcggaagcgtcagtg tttccatgttatgg 1322 AAGAAGAGGCTGAGTGCGTCCCTGA 1323 GTCCCTGATAACTGCGTCTAAGACC 1324 GCCGGCACGGGCATTGGGAAACAGC 1325 AGGATAAAGTCATCCCCAAGGCTCC 1326 AAGGCTCCAGCTACTCTAAATTATG 1327 CCAGGAGATTGTCCTTCATCGTCCA 1328 CTCCCACGTGGTTGCAGATACCTCA 1329 TGCAGATACCTCAGACCTGGTGCTC 1330 CATCCAAGCGGGGGCCACTTGAGAA 1331 AAGCGTCAGTGTTTCCATGTTATGG CRTC3 218648_at 1332 CCAGTTGTGGTCCTCAGCATTTGAA ccagttgtggtcctcagcatttgaagcagctgcatacttcagagtaaactatt NM_022769.1 tttcattatttagttttgtcacaagaaatcgaccattgtactactctcactta cagcagttaaacagcatagaactaaaaacctgtctgcatttccattttttctt tctgtatggttgtgggttttaggacatagggggttaggagaaggggtttcttg atcatgtcatgaattctcctttgtcctgtttctcctgtttcatttctcctccg cctgctgtatattacctgagctggtgttgtatcttcaagtccatatgcgtatt tgcagacctttcctgttcccactcttgttggctcttctgatttatgcacagat ggttcccagcatgtgtccagtgcttcatggatgggaccatcccagcaactaat cagacttcctgccagtgtcctaacccccagggcaccctgttcaaccatatttaaa 1333 GAAATCGACCATTGTACTACTCTCA 1334 GTACTACTCTCACTTACAGCAGTTA 1335 AAAACCTGTCTGCATTTCCATTTTT 1336 GAGCTGGTGTTGTATCTTCAAGTCC 1337 TATGCGTATTTGCAGACCTTTCCTG 1338 CTCTTGTTGGCTCTTCTGATTTATG 1339 GATTTATGCACAGATGGTTCCCAGC 1340 CCCAGCATGTGTCCAGTGCTTCATG 1341 ACTAATCAGACTTCCTGCCAGTGTC 1342 GGCACCCTGTTCAACCATATTTAAA PRKCH 218764_at 1343 CACCAAGACGACTGCTTCAGCTTCT caccaagacgactgcttcagcttcttctcttatccttactttctttaatagat NM_024064.1 atttattaaactgtccagtgaaaaggtgccacaatgcccagtattgtaaacaa caggtttgcattcatgaagctttcattcattctggagtctactaatttacctg aatggtgtttgcattctgtgaaatgcctctccacgttgcatatgtcacacttt tgtctgcacataactcttttttcacaagaagggtcactgccacaacagcacag tcagcgggtgaattacaggtgcctgctgcctgcctacctgggtaatctgatct tgtctgtatcgccgtgtgctcatcactgaagaattgcaggccactcatgtcagt 1344 TCTCTTATCCTTACTTTCTTTAATA 1345 AAAGGTGCCACAATGCCCAGTATTG 1346 AGCTTTCATTCATTCTGGAGTCTAC 1347 ATTCTGTGAAATGCCTCTCCACGTT 1348 TCTCCACGTTGCATATGTCACACTT 1349 GTCTGCACATAACTCTTTTTTCACA 1350 GCCACAACAGCACAGTCAGCGGGTG 1351 GTCAGCGGGTGAATTACAGGTGCCT 1352 GTAATCTGATCTTGTCTGTATCGCC 1353 AGAATTGCAGGCCACTCATGTCAGT CHST12 218927_s_at 1354 GACCCGCACACGGAGAAGCTGGCGC gacccgcacacggagaagctggcgcccttcaacgagcactggcggcaggtgta NM_018641.1 ccgcctctgccacccgtgccagatcgactacgacttcgtggggaagctggaga ctctggacgaggacgccgcgcagctgctgcagctactccaggtggaccggcag ctccgcttccccccgagctaccggaacaggaccgccagcagctgggaggagga ctggttcgccaagatccccctggcctggaggcagcagctgtataaactctacg aggccgactttgttctcttcggctaccccaagcccgaaaacctcctccgagac tgaaagctttcgcgttgctttttctcgcgtgcctggaacctgacgcacgcgca ctccagtttttttatgacctacgattttgcaatctgggcttcttgttcactccactg cctctatccattgagtac 1355 CACTGGCGGCAGGTGTACCGCCTCT 1356 GCCAGATCGACTACGACTTCGTGGG 1357 GCTGGAGACTCTGGACGAGGACGCC 1358 GGAGGAGGACTGGTTCGCCAAGATC 1359 TAAACTCTACGAGGCCGACTTTGTT 1360 GAAAACCTCCTCCGAGACTGAAAGC 1361 AAAGCTTTCGCGTTGCTTTTTCTCG 1362 GCGTGCCTGGAACCTGACGCACGCG 1363 TTTGCAATCTGGGCTTCTTGTTCAC 1364 TCCACTGCCTCTATCCATTGAGTAC C16ORF68 218945_at 1365 ACTGGACTGGCTGAAGGACGACCTC actggactggctgaaggacgacctctgcacagatcccaaggtccccttcagtt NM_024109.1 ggtcacaagaggaaatttctgacctgtacgatcacaccaccatcctgtttgca gccgaagtgttttacgacgacgacttgactgatgctgtgtttaaaacgctctc ccgactcgcccacagattgaaaaatgcctgcacagccatactgtcggtggaga agaggctcaacttcacactgagacacttggacgtcacatgtgaagcctacgat cacttccgctcctgcctgcacgcgctggagcagctcacagatggcaagctgcg cttcgtggtggagcccgtggaggcctccttcccacagctcctggtttacgagc gcctccagcagctggagctctggaagatcatcgcagaaccagtaacatgacccatcg cctccaccaggcgcggcgtctcgactgttcttagagtg 1366 AATTTCTGACCTGTACGATCACACC 1367 ACCATCCTGTTTGCAGCCGAAGTGT 1368 TACGACGACGACTTGACTGATGCTG 1369 TGCTGTGTTTAAAACGCTCTCCCGA 1370 CCTGCACAGCCATACTGTCGGTGGA 1371 ATGTGAAGCCTACGATCACTTCCGC 1372 GCTCACAGATGGCAAGCTGCGCTTC 1373 TCCCACAGCTCCTGGTTTACGAGCG 1374 CAGAACCAGTAACATGACCCATCGC 1375 CGGCGTCTCGACTGTTCTTAGAGTG TTC17 218972_at 1376 CTCCTGGGCCACAAGGGCTACTAGA ctcctgggccacaagggctactagactggaagaccaggaaagtgccatagaca NM_018259.1 taatgtaactggatttcagcaaggcatttaacagagcctcttatgatatcctt gtgaaccagatggagagatgtgggcttgaagccttcccattgcctacaggata aaattcaaacttcctagtgtggtgtacaagaccctttacagcccgcctctgtg tacccttcaacaccattctctgaaccaaccatgctcatgtttttacctcagtg cctttgcacatgctattccctctgcctggaatgccctgtgccccctctgccct ctgccgtgctaaaatatcactcatccttaaacttcaaaatcaagtgccatctc ttccttgttaccttcaggcagaattagttactctttcctctgtgcaattgttc tatatcttcgctctagctcttttcctgttgtattgtaatgatttgtttatgtt taccttccttactagactgtgagctcaagagcaggccgtcttaattattcctttctg tacccctagtgtcttttatggttctcagccc 1377 CAGAGCCTCTTATGATATCCTTGTG 1378 GATGTGGGCTTGAAGCCTTCCCATT 1379 TGGTGTACAAGACCCTTTACAGCCC 1380 TGCCCTCTGCCGTGCTAAAATATCA 1381 CTCTTCCTTGTTACCTTCAGGCAGA 1382 AGAATTAGTTACTCTTTCCTCTGTG 1383 GTGCAATTGTTCTATATCTTCGCTC 1384 TTATGTTTACCTTCCTTACTAGACT 1385 GCAGGCCGTCTTAATTATTCCTTTC 1386 TAGTGTCTTTTATGGTTCTCAGCCC PLEKHA1 219024_at 1387 ACTCTTTGGTCTCAACCTTTACCAT acaacgtctcgaactttctatgtgcaggctgatagccctgaagagatgcacag NM_021622.1 ttggattaaagcagtctctggcgccattgtagcacagcggggtcccggcagat ctgcgtcttctgagcatccccccggtccttcagaatccaaacacgctttccgt cctaccaacgcagccgccgccacctcacattccacagcctctcgcagcaactc tttggtctcaacctttaccatggagaagcgaggattttacgagtctcttgcca aggtcaagccagggaacttcaaggtccagactgtctctccaagagaaccagct tccaaagtgactgaacaagctctgttaagacctcaaagtaaaaatggccctca ggaaaaagattgtgacctagtagacttggacgatgcgagccttccggtcagtg acgtgtgaggcagaagcgcacggagcctgcctgcctctgccgtcctcagttacctttc atgaggcttctagcc 1388 GGATTTTACGAGTCTCTTGCCAAGG 1389 TTCAAGGTCCAGACTGTCTCTCCAA 1390 TCTCTCCAAGAGAACCAGCTTCCAA 1391 AGTAGACTTGGACGATGCGAGCCTT 1392 AGCCTTCCGGTCAGTGACGTGTGAG 1393 GAGGCAGAAGCGCACGGAGCCTGCC 1394 GTTACCTTTCATGAGGCTTCTAGCC 1395 ACAACGTCTCGAACTTTCTATGTGC 1396 CTCTGGCGCCATTGTAGCACAGCGG 1397 TCAGAATCCAAACACGCTTTCCGTC GIMAP4 219243_at 1398 TCTTCTAGATTCTCTCTATGTTGGC tcttctagattctctctatgttggcagataatctccccttgtagcttccactc NM_018326.1 acttattcttgcattcagagtcacaatgatcatcttacccatgtggtttttga gaaagaaagatcaattctttgtttgcagtgggtaatcttagagatggagatga ttgtagaattattcctagatgagtgtcaatttatttaattccattgtcatata aggagtcaaattgtttcttatcatttgttcattgaagaacagagacctgtctg gaaaatcgatctctacaaattcaattaaataatgatccccaaatgctgaaaaa gtgaaatacagcaattcaacagataatagagcaatgtttagtatattcagctg tatctgtagaaactctttgacgaacctcaatttaaccaatttgatgaataccc agttctcttcttttctagagaaagatagttgcaacctcacctccctcactcaacactt tgaatacttattgtttggcaggtcatccacacact 1399 TGTTGGCAGATAATCTCCCCTTGTA 1400 TTCCACTCACTTATTCTTGCATTCA 1401 GAGTCACAATGATCATCTTACCCAT 1402 GATCAATTCTTTGTTTGCAGTGGGT 1403 AATTGTTTCTTATCATTTGTTCATT 1404 TGTAGAAACTCTTTGACGAACCTCA 1405 TGATGAATACCCAGTTCTCTTCTTT 1406 GAAAGATAGTTGCAACCTCACCTCC 1407 CTCCCTCACTCAACACTTTGAATAC 1408 TTGTTTGGCAGGTCATCCACACACT CENTA2 219358_s_at 1409 CCAGCTACTCCGGACACTGATGTGA ccagctactccggacactgatgtgagaggatcacttgagccagggaggtcatg NM_018404.1 gctacagtgacccctcattgcaccactttacttagcctgggtgacagagtgag accctatctcaaaaaaaaaaaaaatctatgcattgtatgggactttcctttgg atcccccaatcaaaggataagcaatgcgtaagcctgtgtccttcctgaagctt ctcgactgcccagatagggaggtgagtcctctctatctcctctggctctggaa gcaccttgaaaatgtgcattttcaaggacacttgctgggttgtgcattaaggg ccagtttacttgtctgcctctttgaccacctgtgaactctgttgggtgtactctgcta agt 1410 GGGAGGTCATGGCTACAGTGACCCC 1411 TTGCACCACTTTACTTAGCCTGGGT 1412 TATGCATTGTATGGGACTTTCCTTT 1413 AAGCAATGCGTAAGCCTGTGTCCTT 1414 TTCTCGACTGCCCAGATAGGGAGGT 1415 TAGGGAGGTGAGTCCTCTCTATCTC 1416 AAGGACACTTGCTGGGTTGTGCATT 1417 GGTTGTGCATTAAGGGCCAGTTTAC 1418 TTGACCACCTGTGAACTCTGTTGGG 1419 CTCTGTTGGGTGTACTCTGCTAAGT SERTAD3 219382_at 1420 TTTGTTCCCATTTCAGGGTTCCACA tgtgtttttgtgggggctcgaagcagtgactatggcctcctttgttcccattt NM_013368.1 cagggttccacaaactgtcttgcatgtgtgtgtgtgtctggttaccccgacct tctgtgaaggtgggtcttcctgaattaatttatctattccaaatgccttaacg agactctgtttctgggagtctgattttccacttacacatttcttccacctttc ctgctagttcccactcccctgtgaccactggggcctcagggaagataaagaaa gctgggcctgtcgaaggatgacagggatgtgctgccaggttgctatagaaacc caggctctgcctcttgcaccttgagggggtgggaggggctggtgtcctccctc caggctgaaccccacttcctcggcaggaccccagtctcagcagcctcctgatt tcataaccaggccggaccacgtgcaatagggtggaaaccaaactgctccatgccggg ttatttaaaagaaaggcagagtttgtggtggcttttttt 1421 TCAGGGTTCCACAAACTGTCTTGCA 1422 GCCTTAACGAGACTCTGTTTCTGGG 1423 TGATTTTCCACTTACACATTTCTTC 1424 GGATGTGCTGCCAGGTTGCTATAGA 1425 GCCTCTTGCACCTTGAGGGGGTGGG 1426 TGATTTCATAACCAGGCCGGACCAC 1427 ACTGCTCCATGCCGGGTTATTTAAA 1428 GGCAGAGTTTGTGGTGGCTTTTTTT 1429 TGTGTTTTTGTGGGGGCTCGAAGCA 1430 GCTCGAAGCAGTGACTATGGCCTCC HPSE 219403_s_at 1431 ATTGGGCCTGTCAGCCCGAATGGGA attgggcctgtcagcccgaatgggaatagaagtggtgatgaggcaagtattct NM_006665.1 ttggagcaggaaactaccatttagtggatgaaaacttcgatcctttacctgat tattggctatctcttctgttcaagaaattggtgggcaccaaggtgttaatggc aagcgtgcaaggttcaaagagaaggaagcttcgagtataccttcattgcacaa acactgacaatccaaggtataaagaaggagatttaactctgtatgccataaac ctccataatgtcaccaagtacttgcggttaccctatcctttttctaacaagca agtggataaataccttctaagacctttgggacctcatggattactttccaaat ctgtccaactcaatggtctaactctaaagatggtggatgatcaaaccttgcca cctttaatggaaaaacctctccggccaggaagttcactgggcttgccagctttctca tatagtttttttgtgataagaaatgccaaagttgctgcttgcatctga 1432 GAAAACTTCGATCCTTTACCTGATT 1433 GATTATTGGCTATCTCTTCTGTTCA 1434 AGCTTCGAGTATACCTTCATTGCAC 1435 AACTCTGTATGCCATAAACCTCCAT 1436 CAAGTACTTGCGGTTACCCTATCCT 1437 GACCTTTGGGACCTCATGGATTACT 1438 GATTACTTTCCAAATCTGTCCAACT 1439 GAAGTTCACTGGGCTTGCCAGCTTT 1440 GCCAGCTTTCTCATATAGTTTTTTT 1441 TGCCAAAGTTGCTGCTTGCATCTGA CLIC3 219529_at 1442 ACGCCAAGACAGACACGCTGCAGAT acgccaagacagacacgctgcagatcgaggactttctggaggagacgctgggg NM_004669.1 ccgcccgacttccccagcctggcgcctcgttacagggagtccaacaccgccgg caacgacgttttccacaagttctccgcgttcatcaagaacccggtgc 1443 AGACACGCTGCAGATCGAGGACTTT 1444 ACACGCTGCAGATCGAGGACTTTCT 1445 GCTGCAGATCGAGGACTTTCTGGAG 1446 CGAGGACTTTCTGGAGGAGACGCTG 1447 GCCTCGTTACAGGGAGTCCAACACC 1448 TCGTTACAGGGAGTCCAACACCGCC 1449 GCAACGACGTTTTCCACAAGTTCTC 1450 CAAGTTCTCCGCGTTCATCAAGAAC 1451 TTCTCCGCGTTCATCAAGAACCCGG 1452 TCCGCGTTCATCAAGAACCCGGTGC PLEKHF1 219566_at 1453 TTGGTAACAAACGCCACCTTACACT ttggtaacaaacgccaccttacactctgcaggctgcagcggcagctccagatg NM_024310.1 gcctcctgagctggacgaccccaggtctccagacatctagggaccagagcagg tttgggaacacagagggaagacaggatgggagtgtagccacagaacccacctg caccctgacaggcacaccccactgaagagcctgagtcccaggaggcctcctgg aagcccaggactgcccacccaccacgctggtgcccaccgcctggccagccaag ccctgccgatcagacatgtgggctccccgaagcccagccagagactgccgtgc tgtgggtgccaccaggcccagggactgcagcctgagctccccgaggcccaggg cagccgggtgaggactctgtcctgtgtcacctctctccaggtgtccagctgtc tcatgcctttttgtcctgtcctcagctctccgtgtggtcagcgaaaccattgttttct gttaggactcagttgcaa 1454 CCCAGGTCTCCAGACATCTAGGGAC 1455 ATCTAGGGACCAGAGCAGGTTTGGG 1456 TGGGAGTGTAGCCACAGAACCCACC 1457 CAGGCACACCCCACTGAAGAGCCTG 1458 CCCACTGAAGAGCCTGAGTCCCAGG 1459 AAGCCCTGCCGATCAGACATGTGGG 1460 CAGCCAGAGACTGCCGTGCTGTGGG 1461 CTCTCCGTGTGGTCAGCGAAACCAT 1462 GTCAGCGAAACCATTGTTTTCTGTT 1463 GTTTTCTGTTAGGACTCAGTTGCAA CLDN15 219640_at 1464 CCTCCAGGCCAAGAACTGCTCTTGG taccccggaaccaagtacgagctgggccccgccctctacctggggtggagcgc NM_014343.1 ctcactgatctccatcctgggtggcctctgcctctgctccgcctgctgctgcg gctctgacgaggacccagccgccagcgcccggcggccctaccaggctcccgtg tccgtgatgcccgtcgccacctcggaccaagaaggcgacagcagctttggcaa atacggcagaaacgcctacgtgtagcagctctggcccgtgggccccgctgtct tcccactgccccaaggagaggggacctggccggggcccattcccctatagtaa cctcaggggccggccacgccccgctcccgtagccccgccccggccacggcccc gtgtcttgcactctcatggcccctccaggccaagaactgctcttgggaagtcg catatctcccctctgaggctggatccctcatcttctgaccctgggttctgggctgtg aaggggacggtgtccccgcacgtttgtattgtgtat 1465 TCTTGGGAAGTCGCATATCTCCCCT 1466 TCATCTTCTGACCCTGGGTTCTGGG 1467 TGACCCTGGGTTCTGGGCTGTGAAG 1468 GTGAAGGGGACGGTGTCCCCGCACG 1469 GTCCCCGCACGTTTGTATTGTGTAT 1470 TACCCCGGAACCAAGTACGAGCTGG 1471 GTCGCCACCTCGGACCAAGAAGGCG 1472 GACCAAGAAGGCGACAGCAGCTTTG 1473 GAAACGCCTACGTGTAGCAGCTCTG 1474 CTTCCCACTGCCCCAAGGAGAGGGG SIDT1 219734_at 1475 GAGAAGTTCTACATTGACCAGGCCC gagaagttctacattgaccaggcccccttgttgcctggagtatgacgtaatca NM_017699.1 gaaaatagacgtataaatgtgcacatgcgtatgtatttgcttgtgaaattaaa gtcacctcttgcctctgctttcctgatcattcgttagagaaatggatcaggca tttttttaaattattattctttctctaaactatttgcattgtgttcaaaaacc cattttagaagtttgaacagcaagcttttcctgattttaaaaacacaaagttg ctttcaatgaaatattttgtgatttttttaaagtccccaaatgtgtacttagc cttctgttattccttattctttaagcagtgttggcttccattgaccatatgaaggcc accaattaaatggttgtg 1476 CCCCTTGTTGCCTGGAGTATGACGT 1477 GTGCACATGCGTATGTATTTGCTTG 1478 CTGCTTTCCTGATCATTCGTTAGAG 1479 TGCATTGTGTTCAAAAACCCATTTT 1480 GAACAGCAAGCTTTTCCTGATTTTA 1481 GTCCCCAAATGTGTACTTAGCCTTC 1482 TACTTAGCCTTCTGTTATTCCTTAT 1483 GTTATTCCTTATTCTTTAAGCAGTG 1484 CAGTGTTGGCTTCCATTGACCATAT 1485 GAAGGCCACCAATTAAATGGTTGTG PVRIG 219812_at 1486 GCCCAGGGCCATGGAAGGACCCTTA gctttgtctctgttgagaatggactctacgctcaggcaggggagaggcctcct NM_024070.1 cacactggtcccggcctcactcttttccctgaccctcgggggcccagggccat ggaaggacccttaggagttcgatgagagagaccatgaggccactgggctttcc ccctcccaggcctcctgggtgtcatccccttactttaattcttgggcctccaa taagtgtcccataggtgtctggccaggcccacctgctgcggatgtggtctgtg tgcgtgtgtgggcacaggtgtgagtgtgtgagtgacagttaccccatttcagtcattt cctgctgcaac 1487 AGGACCCTTAGGAGTTCGATGAGAG 1488 TCATCCCCTTACTTTAATTCTTGGG 1489 TTCTTGGGCCTCCAATAAGTGTCCC 1490 TAAGTGTCCCATAGGTGTCTGGCCA 1491 GTGCGTGTGTGGGCACAGGTGTGAG 1492 TGTGAGTGACAGTTACCCCATTTCA 1493 GACAGTTACCCCATTTCAGTCATTT 1494 CATTTCAGTCATTTCCTGCTGCAAC 1495 GCTTTGTCTCTGTTGAGAATGGACT 1496 TGAGAATGGACTCTACGCTCAGGCA GFOD1 219821_s_at 1497 GATTGATTGGGCTTCCTCATAGGAA gattgattgggcttcctcataggaagcactgagggtgtgtctttgtacttggt NM_018988.1 tcattgcccttcacctggtagagaaagagaggtcagaaatagcaagcaaaaag caggactcccaggagccacaagaaaagagcacaggctgcaccaaagcaggggc agcagagaataaaatatccctttgaacttgtcaacaattaaaaaactgcaagg agtcaccttataacactatttccagtaaaggtggaattgagtatcagagggat tactgcggtgttaaggtagccctgccacgtggctctccaggcagggccaagaa gacagcacaaagtatgggtttggccataagctcatatgctgcccccaaagact ggggagagctgtgtgcctcagtgttgcagtgtgaattcctaaatagagggtaa agtgagcctagccaggaggtgtttggggctctatcgcgcatctctcctaccaa gctgggcaagagcttttaggagattcatccagctttgtggatttagaaaggaagcctt cagttccaatcagaatc 1498 GTGTCTTTGTACTTGGTTCATTGCC 1499 TCATTGCCCTTCACCTGGTAGAGAA 1500 GTCACCTTATAACACTATTTCCAGT 1501 CTGCGGTGTTAAGGTAGCCCTGCCA 1502 TGGCTCTCCAGGCAGGGCCAAGAAG 1503 TTGGCCATAAGCTCATATGCTGCCC 1504 AGACTGGGGAGAGCTGTGTGCCTCA 1505 GTGTGCCTCAGTGTTGCAGTGTGAA 1506 CAGGAGGTGTTTGGGGCTCTATCGC 1507 GAAGCCTTCAGTTCCAATCAGAATC LUC7L2 220099_s_at 1508 GATGCTGATCTCTTTATTCTTTCAA gatgctgatctctttattctttcaagtaagagtgctagtgaacaaattgtgtt NM_016007.1 acttggccttgggattttttgaacgtttgtaaaatgctgtcttcctagtccaa acagctgcagctttgggcatttttctttttaattattcttcctctgactttgt atcccttaatacctacactctccaattgtaagagaaagggggcagggaagcaa tatagcttccattctaaggctgtattcccgttatgaattactagctgattaca gttcagagcattgatcctggaatgtgtgctggagaaatttaaaatactggggt tttttgtttaatggtgcctatttagagttggaagttgaacagctgttgcatta catacttttgcttttttattgaaattttgaaatcaaacgtcttgatttttctg ttctgttgaattgctatgttcaggatgttctagggggtgggggcagggactcttttcg taataag 1509 AATGCTGTCTTCCTAGTCCAAACAG 1510 AGCTGCAGCTTTGGGCATTTTTCTT 1511 AATTATTCTTCCTCTGACTTTGTAT 1512 TCCTCTGACTTTGTATCCCTTAATA 1513 CTTAATACCTACACTCTCCAATTGT 1514 AAGGCTGTATTCCCGTTATGAATTA 1515 GAACAGCTGTTGCATTACATACTTT 1516 GATTTTTCTGTTCTGTTGAATTGCT 1517 GTTCAGGATGTTCTAGGGGGTGGGG 1518 GGGCAGGGACTCTTTTCGTAATAAG MNAB 220202_s_at 1519 TGGGGTGCGATTTCCAGATCTTCCC tggggtgcgatttccagatcttcccgtacaggttaccataccacagatcctgt NM_018835.1 ccaggccactgcttcccaaggaagtgcgactaagcccatcagtgtatcagatt atgtcccttatgtcaatgctgttgattcaaggtggagttcatatggcaacgag gccacatcatcagcacactatgttgaaagggacagattcattgttactgattt atctggtcatagaaagcattccagtactggggaccttttgagccttgaacttc agcaggccaagagcaactcattacttcttcagagagaggccaatgctttggccatgc aacagaagtggaattccctggatgaaggccgtcac 1520 TTCCCGTACAGGTTACCATACCACA 1521 GTGCGACTAAGCCCATCAGTGTATC 1522 TATGTCCCTTATGTCAATGCTGTTG 1523 GTGGAGTTCATATGGCAACGAGGCC 1524 GCCACATCATCAGCACACTATGTTG 1525 TACTGGGGACCTTTTGAGCCTTGAA 1526 GAGCCTTGAACTTCAGCAGGCCAAG 1527 AGAGCAACTCATTACTTCTTCAGAG 1528 CAATGCTTTGGCCATGCAACAGAAG 1529 GAATTCCCTGGATGAAGGCCGTCAC CECR7 220452_x_at 1530 GATGAGAAAGACCTGACTGTGCCCC gatgagaaagacctgactgtgccccagcccgacacccataaagggtctgtgct NM_021031.1 gaggtggattagtaaaagaggaaagcctcttgcagttgagatagaggaaggcc actgtctctgcctgcccctgggaactgaatgtctcggtataaaaccgattgta catttgttcaattctgagataggagaaaaccgccctatggtgggagcgagaca tgtttcgagcaatgctgccttgttattctttactccgctgagatgtttgggtg gagagaaacataaatctggcctacatgcacatccgggcatagtaccttccctt gaacttaatcatgacacagattcttttgctcacatgttttttgctgaccttct ccttattatcaccctgctgtcctactacattcctttttgctgaaataatgaaa ataatagtcaataaaaactgagggaactcaaaggccggtgccagtgcaggtcc ttggtgtgtcgaatactggtcccc 1531 TAGAGGAAGGCCACTGTCTCTGCCT 1532 GCCCCTGGGAACTGAATGTCTCGGT 1533 GTGGGAGCGAGACATGTTTCGAGCA 1534 AGCAATGCTGCCTTGTTATTCTTTA 1535 ATAAATCTGGCCTACATGCACATCC 1536 AGTACCTTCCCTTGAACTTAATCAT 1537 GACACAGATTCTTTTGCTCACATGT 1538 GCTCACATGTTTTTTGCTGACCTTC 1539 TCAAAGGCCGGTGCCAGTGCAGGTC 1540 CTTGGTGTGTCGAATACTGGTCCCC TH1L 220607_x_at 1541 ACTTCCTGTTGTCAGTTACATCCGA acttcctgttgtcagttacatccgaaagtgtctggagaagctggacactgaca NM_016397.1 tttcactcattcgctattttgtcactgaggtgctggacgtcattgctcctcct tatacctctgacttcgtgcaacttttcctccccatcctggagaatgacagcat cgcaggtaccatcaaaacggaaggcgagcatgaccctgtgacggagtttatag ctcactgcaaatctaacttcatcatggtgaactaatttagagcatcctccaga gctgaagcagaacattccagaacccgttgtggaaaaaccctttcaagaagctg ttttaagaggctcgggcagcgtcttgaaaatgggcaccgctgggaggaggtgg atgacttctttacaaaggaaaatggcaggcgctgggctcccacgacccctcag gacagatctggccgtcagccgcgggccgctgggaactccactcggggaactcctttcc aagctgacctcagttttctcac 1542 GGACACTGACATTTCACTCATTCGC 1543 TCACTCATTCGCTATTTTGTCACTG 1544 GTCACTGAGGTGCTGGACGTCATTG 1545 TTTTCCTCCCCATCCTGGAGAATGA 1546 GAATGACAGCATCGCAGGTACCATC 1547 CGAGCATGACCCTGTGACGGAGTTT 1548 GAGCATCCTCCAGAGCTGAAGCAGA 1549 GCAGAACATTCCAGAACCCGTTGTG 1550 TTAAGAGGCTCGGGCAGCGTCTTGA 1551 TCCAAGCTGACCTCAGTTTTCTCAC KLRF1 220646_s_at 1552 ATCCAGGATTTTTATTCGTCGCTTA atattcttcataaagggaccagctaaagaaaacagctgtgctgccattaagga NM_016523.1 aagcaaaattttctctgaaacctgcagcagtgttttcaaatggatttgtcagt attagagtttgacaaaattcacagtgaaataatcaatgatcactatttttggc ctattagtttctaatattaatctccaggtgtaagattttaaagtgcaattaaa tgccaaaatctcttctcccttctccctccatcatcgacactggtctagcctca gagtaacccctgttaacaaactaaaatgtacacttcaaaatttttacgtgata gtataaaccaatgtgacttcatgtgatcatatccaggatttttattcgtcgct tattttatgccaaatgtgatcaaattatgcctgtttttctgtatcttgcgttt taaattcttaataaggtcctaaacaaaatttcttatatttctaatggttgaat tataatgtgggtttatacattttttacccttttgtcaaagagaattaactttgtttcc aggcttttgctact 1553 TTATTCGTCGCTTATTTTATGCCAA 1554 AATGTGATCAAATTATGCCTGTTTT 1555 ACTTTGTTTCCAGGCTTTTGCTACT 1556 ATATTCTTCATAAAGGGACCAGCTA 1557 ACAGCTGTGCTGCCATTAAGGAAAG 1558 AAATTTTCTCTGAAACCTGCAGCAG 1559 CAATGATCACTATTTTTGGCCTATT 1560 CTCCATCATCGACACTGGTCTAGCC 1561 TAGCCTCAGAGTAACCCCTGTTAAC 1562 GTGACTTCATGTGATCATATCCAGG TBX21 220684_at 1563 TCCTGGCCCACGATGAAACCTGAGA tcctggcccacgatgaaacctgagaggggtgtccccttgccccatcctctgcc NM_013351.1 ctaactacagtcgtttacctggtgctgcgtcttgcttttggtttccagctgga gaaaagaagacaagaaagtcttgggcatgaaggagctttttgcatctagtggg tgggaggggtcaggtgtgggacatgggagcaggagactccactttcttccttt gtacagtaactttcaaccttttcgttggcatgtgtgttaatccctgatccaaa aagaacaaatacacgtatgttataaccatcagcccgccagggtcagggaaagg actcacctgactttggacagctggcctgggctccccctgctcaaacacagtgg ggatcagagaaaaggggctggaaaggggggaatggcccacatctcaagaagcaa 1564 CTCTGCCCTAACTACAGTCGTTTAC 1565 TACAGTCGTTTACCTGGTGCTGCGT 1566 GGAGCTTTTTGCATCTAGTGGGTGG 1567 GGGGTCAGGTGTGGGACATGGGAGC 1568 AACTTTCAACCTTTTCGTTGGCATG 1569 GGCATGTGTGTTAATCCCTGATCCA 1570 CGTATGTTATAACCATCAGCCCGCC 1571 GCCCGCCAGGGTCAGGGAAAGGACT 1572 GAAAGGACTCACCTGACTTTGGACA 1573 GAATGGCCCACATCTCAAGAAGCAA DDX47 220890_s_at 1574 AGCCCAAAGGTTTGCCCGAATGGAG agcccaaaggtttgcccgaatggagttaagggagcatggagaaaagaagaaac NM_016355.1 gctcgcgagaggatgctggagataatgatgacacagagggtgctattggtgtc aggaacaaggtggctggaggaaaaatgaagaagcggaaaggccgttaatcact tttatgaaggctcgagttctgctgttctgtaaaagagaattggagaatgaaac ctgctccaacagagatcatgagactgaaattggtcagaattgtgtccagaatg tgctcagctaattcagtattcttccccattctgggttggagtttactgcagag taattcttacagtgctgatgtcaagactgttactgttcttcgactttgattcc ttgctcatgacatgagtagggtgtgctcttctgtcacttcacacagacctttt gccttttttagctgcaagtcaaggactaggttgatgatgcccatgacctgtaa ttgtaaagaagcttggacatctgcaaatgatatttaaaccatcttggcttgtg ctt 1575 GAAACGCTCGCGAGAGGATGCTGGA 1576 GAGGGTGCTATTGGTGTCAGGAACA 1577 AATTGTGTCCAGAATGTGCTCAGCT 1578 TCAGCTAATTCAGTATTCTTCCCCA 1579 GTTACTGTTCTTCGACTTTGATTCC 1580 GACTTTGATTCCTTGCTCATGACAT 1581 CATGAGTAGGGTGTGCTCTTCTGTC 1582 CTGTCACTTCACACAGACCTTTTGC 1583 GATGATGCCCATGACCTGTAATTGT 1584 ATTTAAACCATCTTGGCTTGTGCTT DENND2D 221081_s_at 1585 TTCTCACTTTTCATCCAGGAAGCCG ttctcacttttcatccaggaagccgagaagagcaagaatcctcctgcaggcta NM_024901.1 tttccaacagaaaatacttgaatatgaggaacagaagaaacagaagaaaccaa gggaaaaaactgtgaaataagagctgtggtgaataagaatgactagagctaca caccatttctggacttcagcccctgccagtgtggcaggatcagcaaaactgtc agctcccaaaatccatatcctcactctgagtcttggtatccaggtattgcttc aaactggtgtctgagatttggatccctggtattgatttctcaggactttggag ggctctgacaccatgctcacagaactgggctcagagctccattttttgcagag gtgacacaggtaggaaacagtagtacatgtgttgtagacacttggttagaagc tgctgcaactgccctctcccatcattataacatcttcaacacagaacacactt tgtggtcgaaaggctcagcctctctacatgaagtctg 1586 AAGAGCAAGAATCCTCCTGCAGGCT 1587 GAGCTACACACCATTTCTGGACTTC 1588 GGATCAGCAAAACTGTCAGCTCCCA 1589 ATCCTCACTCTGAGTCTTGGTATCC 1590 GGTGTCTGAGATTTGGATCCCTGGT 1591 GACACCATGCTCACAGAACTGGGCT 1592 GGCTCAGAGCTCCATTTTTTGCAGA 1593 TGGTTAGAAGCTGCTGCAACTGCCC 1594 TTTGTGGTCGAAAGGCTCAGCCTCT 1595 GCTCAGCCTCTCTACATGAAGTCTG LOC339047 221501_x_at 1596 TGATAACTCCCTGAGCCTCAAGACA gaatggcggcagtggagcatcgtcattcttcaggattgccctactggccctac AF229069.1 ctcacagctgaaactttaaaaaacaggatgggccaccagccacctcctccaac tcaacaacattctataattgataactccctgagcctcaagacaccttccgagt gtgtgctctatccccttccaccctcagcggatgataatctcaagacacctccc gagtgtctgctcactccccttccaccctcagctctaccctcagcggatgataa tctcaagacacctgccgagtgcctgctctatccccttccaccctcagcggatg ataatctcaagacacctcccgagtgtctgctcactccccttccaccctcagctccac cctcagcggatgataatctcaagacacctcctgagtgtgtctgctca 1597 AGACACCTTCCGAGTGTGTGCTCTA 1598 GAATGGCGGCAGTGGAGCATCGTCA 1599 CCTTCCACCCTCAGCGGATGATAAT 1600 TGATAATCTCAAGACACCTCCCGAG 1601 AGCTCTACCCTCAGCGGATGATAAT 1602 TAATCTCAAGACACCTGCCGAGTGC 1603 GATGATAATCTCAAGACACCTCCCG 1604 CATCGTCATTCTTCAGGATTGCCCT 1605 GCTCCACCCTCAGCGGATGATAATC 1606 GACACCTCCTGAGTGTGTCTGCTCA PYCARD 221666_s_at 1607 CTGGATGCGCTGGAGAACCTGACCG ctggatgcgctggagaacctgaccgccgaggagctcaagaagttcaagctgca BC004470.1 ggcggccacgcaccagggctctggagccgcgccagctgggatccaggcccctc ctcagtcggcagccaagccaggcctgcactttatagaccagcaccgggctgcg cttatcgcgagggtcacaaacgttgagtggctgctggatgctctgtacgggaa ggtcctgacggatgagcagtaccaggcagtgcgggccgagcccaccaacccaa gcaagatgcggaagctcttcagtttcacaccagcctggaactggacctgcaaggact tgctcctccaggccctaagggagtcccagtcctacctggtggaggac 1608 GGCCTGCACTTTATAGACCAGCACC 1609 GCGCTTATCGCGAGGGTCACAAACG 1610 GTCACAAACGTTGAGTGGCTGCTGG 1611 CTGCTGGATGCTCTGTACGGGAAGG 1612 GTACGGGAAGGTCCTGACGGATGAG 1613 TGAGCAGTACCAGGCAGTGCGGGCC 1614 TGCGGAAGCTCTTCAGTTTCACACC 1615 GGAACTGGACCTGCAAGGACTTGCT 1616 CTCCAGGCCCTAAGGGAGTCCCAGT 1617 GTCCCAGTCCTACCTGGTGGAGGAC IMP3 221688_s_at 1618 TCAATAAATGCCCCAACTGCTTTGT gcgcagcatggaggactttgtcacttgggtggactcgtccaagatcaagcggc AL136913.1 acgtgctagagtacaatgaggagcgcgatgacttcgatctggaagcctagcgg atctcccactttgcatggctgtcttttacagatgggaaaactgaggcctgatg ctggagattctatgagggtgctctcctcaagggtatcagacggtcgtaggttc ttaagaatttgattcatcagtggcaggccatgcatagagccacgggaggtgcg tccttgttttccaggaaatgttcttagaacttggactactgattattaattga ctgtgccttgggaaacagtgggaagtaacttggtgcagcactggggtattgtt ggactggttcaattcgtttaactcgaattcttgctcctggccgtggttaagct gtgtacagatgatggagagtttggcctcaagtttttataaactgagcgagact agtgttcaggatctcctcccttgtttaaatgtcaataaatgccccaactgctttgt 1619 GCGCAGCATGGAGGACTTTGTCACT 1620 TTTGTCACTTGGGTGGACTCGTCCA 1621 GACTCGTCCAAGATCAAGCGGCACG 1622 GGAGCGCGATGACTTCGATCTGGAA 1623 CCCACTTTGCATGGCTGTCTTTTAC 1624 GAGGCCTGATGCTGGAGATTCTATG 1625 GGTGCTCTCCTCAAGGGTATCAGAC 1626 GCATAGAGCCACGGGAGGTGCGTCC 1627 CTCCTGGCCGTGGTTAAGCTGTGTA 1628 ATCTCCTCCCTTGTTTAAATGTCAA CSPG2 221731_x_at 1629 TTTCAGCACCGATGGCCATGTAAAT tttcagcaccgatggccatgtaaataagatgatttaatgttgattttaatcct J02814.1 gtatataaantaaaaagtncncaatgagtttngggcatatttaatgatgatta tggagccttagaggtctttaatcattggttcnggctgcttttatgtagtttag gctggaaatggtttcacttgctctttgactgtcagcaagactgaagatggctt ttcctggacagctagaaaacacaaaatcttgtaggtcattgcacctatctcag ccataggtgcagtttgcttctacatgatgctaaaggctgcgaatgggatcctg atggaactaaggactccaatgtcgaactcttctttgctgcattcctttttctt cacttacaagaaaggcctgaatggaggacttttctgtaaccaggaacattttt taggggtcaaagtgctaataattaactcaaccaggtctactttttaatggctt tcataacactaactcataaggttaccgatcaatgcatttcatacggatatagacctag ggctctggagggtgggg 1630 GAAATGGTTTCACTTGCTCTTTGAC 1631 GAAGATGGCTTTTCCTGGACAGCTA 1632 TGTAGGTCATTGCACCTATCTCAGC 1633 GGTGCAGTTTGCTTCTACATGATGC 1634 GGCTGCGAATGGGATCCTGATGGAA 1635 CCAATGTCGAACTCTTCTTTGCTGC 1636 CATTCCTTTTTCTTCACTTACAAGA 1637 GGTCTACTTTTTAATGGCTTTCATA 1638 AAGGTTACCGATCAATGCATTTCAT 1639 AGACCTAGGGCTCTGGAGGGTGGGG GNLY 37145_at 1640 TCCTTGCAGCCATGCTCCTGGGCAA tccttgcagccatgctcctgggcaacccaggtctggtcttntctcgtctgagc M85276 ccnnngtacnacgancnngcaagancccacctnnntgntgaggagaaatcctn gcccgtgncnngnccaggaggnnccnnnnnnnnnnnnnnngaccaaaacacag gnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn nnnnnnggataagcccacccagagaagtgtttccaatgctgcgacccgggtgt gtaggacggggaggtcacgatggcgcgacgtctgcagaaatttcatgaggagg tatcagtctagagttacccagggcctcgtggccggagaaactgcccagcagat ctgtgaggacctcaggttgtgtataccttctacaggtcccctctgagccctctcacc ttgtcctgtggaagaagcacag 1641 ATGCTCCTGGGCAACCCAGGTCTGG 1642 TGCTCCTGGGCAACCCAGGTCTGGT 1643 CCACCCAGAGAAGTGTTTCCAATGC 1644 CACCCAGAGAAGTGTTTCCAATGCT 1645 GAGAAGTGTTTCCAATGCTGCGACC 1646 TGTTTCCAATGCTGCGACCCGGGTG 1647 TCCAATGCTGCGACCCGGGTGTGTA 1648 CACGATGGCGCGACGTCTGCAGAAA 1649 GCGCGACGTCTGCAGAAATTTCATG 1650 GACGTCTGCAGAAATTTCATGAGGA 1651 GTATCAGTCTAGAGTTACCCAGGGC 1652 TGCCCAGCAGATCTGTGAGGACCTC 1653 ATACCTTCTACAGGTCCCCTCTGAG 1654 GCCCTCTCACCTTGTCCTGTGGAAG 1655 ACCTTGTCCTGTGGAAGAAGCACAG TMEM161A 43977_at 1656 CCTCATCTGGTGGACGGCTGCCTGC cctcatctggtggacggctgcctgccagctgctcgccagccttttcggcctct AI660497 acttccaccagcacttggcaggctcctagctgcctgcagaccctcctggggcc ctgaggtctgttcctggggcagcgggacactagcctgccccctctgtttgcgc ccccgtgtccccagctgcaaggtggggccggactccccggcgttcccttcacc acagtgcctgacccgcggccccccttggacgccgagtttctgcctcagaactg tctctcctgggcccagcagcatgagggtcccgaggccattgtctccgaagcgt atgtgccaggtttgagtggcgagggtgatgctggctgctcttctgaacaaataaag 1657 CTCATCTGGTGGACGGCTGCCTGCC 1658 TACTTCCACCAGCACTTGGCAGGCT 1659 CCAGCACTTGGCAGGCTCCTAGCTG 1660 CTTGGCAGGCTCCTAGCTGCCTGCA 1661 TCCTGGGGCCCTGAGGTCTGTTCCT 1662 CCCTGAGGTCTGTTCCTGGGGCAGC 1663 CCCGTGTCCCCAGCTGCAAGGTGGG 1664 TGGACGCCGAGTTTCTGCCTCAGAA 1665 GTTTCTGCCTCAGAACTGTCTCTCC 1666 CATTGTCTCCGAAGCGTATGTGCCA 1667 CTCCGAAGCGTATGTGCCAGGTTTG 1668 CCGAAGCGTATGTGCCAGGTTTGAG 1669 CGAGGGTGATGCTGGCTGCTCTTCT 1670 TGATGCTGGCTGCTCTTCTGAACAA 1671 TGGCTGCTCTTCTGAACAAATAAAG 

What is claimed is:
 1. A method for treating a subject having cancer with an immunotherapeutic agent, comprising determining expression level of at least one gene in a blood sample obtained from the subject, wherein the at least one gene is selected from a first group of genes as listed in Table 2 and a second group of genes as listed in Table 3; determining likelihood of clinical response of the subject to the treatment based on the expression level of the at least one gene in the blood sample, wherein the expression level of the at least one gene selected from the first group of genes is positively correlated with the likelihood of clinical response, and wherein the expression level of the at least one gene selected from the second group of genes is negatively correlated with the likelihood of clinical response; and administering to the subject a therapeutically effective amount of the immunotherapeutic agent for treating the cancer.
 2. The method claim 1, wherein the at least one gene is selected from IL2RB, KLRK1, G3BP, PPP1R16B, CLIC3, PRF1, SPON2, HOP, GNLY, TMEM161A, PRKCH, RUNX3, EOMES, SLC25A5, GZMB, IMP3, and ZAP70, wherein the expression level of the at least one gene is positively correlated with the likelihood of clinical response.
 3. The method claim 1, wherein the at least one gene is selected from ASGR1, ASGR2, CENTA2, PGLS, MAPBPIP, STX10, C16ORF68, and RAB31, wherein the expression level of the at least one gene is negatively correlated with the likelihood of clinical response.
 4. The method claim 1, wherein the expression level of at least two genes in the blood sample is determined, and wherein determining the likelihood of clinical response is based on the expression level of the at least two genes in the blood sample.
 5. The method of claim 4, wherein a first gene of the at least two genes is selected from the first group of genes as listed in Table 2, and a second gene of the at least two genes is selected from the second group of genes as listed in Table
 3. 6. The method of claim 5, wherein the first gene is selected from IL2RB, KLRK1, G3BP, PPP1R16B, CLIC3, PRF1, SPON2, HOP, GNLY, TMEM161A, PRKCH, RUNX3, EOMES, SLC25A5, GZMB, IMP3, and ZAP70.
 7. The method of claim 5, wherein the second gene is selected from ASGR1, ASGR2, CENTA2, PGLS, MAPBPIP, STX10, C16ORF68, and RAB31.
 8. The method of claim 5, wherein the first gene is IL2RB and the second gene is selected from ASGR1 and ASGR2.
 9. The method of claim 8, wherein the first gene is IL2RB and the second gene is ASGR2.
 10. The method of claims 4, wherein determining the likelihood of clinical response comprises subjecting the expression level of the at least two genes to a formula to calculate a score, wherein the formula is pre-determined by statistical analysis of (a) clinical response of a plurality of patients having the cancer to treatment with the immunotherapeutic agent and (b) the expression level of the at least two genes in pre-treatment blood samples from the plurality of patients.
 11. The method of claim 10, wherein a first gene of the at least two genes is selected from the first group of genes as listed in Table 2, and a second gene of the at least two genes is selected from the second group of genes as listed in Table 3, wherein the formula for calculating the score is Score=−C ₁ *X _(first gene) +C ₂ *X _(second gene), wherein X_(first gene) and X_(second gene) are normalized mRNA expression level of the first and the second gene, respectively, and C1 and C2 are each, independently, a number ranging from 0.01 to 3, and wherein the score is negatively correlated with the likelihood of clinical response.
 12. The method of claim 11, wherein C₁ ranges from 0.1 to 2, and C₂ ranges from 0.1 to 1.5.
 13. The method of claim 11, wherein the first gene is IL2RB, and the second gene is ASGR2, and wherein C₁ ranges from 0.2 to 1.5, and C₂ ranges from 0.1 to
 1. 14. The method of claim 11, wherein the score is compared to a predetermined threshold, wherein a score that is lower than the threshold is indicative of high likelihood of clinical response, and a score that is higher than the threshold is indicative of low likelihood of clinical response.
 15. The method of any of claims 1-14, wherein the expression level of the at least one gene is measured by at least one method selected from microarray, quantitative polymerase chain reaction (qPCR), and flow cytometry.
 16. The method of any one of claims 1-15, wherein the immunotherapeutic agent is an anti-CTLA4 antibody.
 17. The method of claim 16, wherein the anti-CTLA4 antibody is ipilimumab.
 18. The method of any one of claims 1-17, wherein the cancer is selected from melanoma, prostate cancer, lung cancer, ovarian cancer, gastric cancer, and glioblastoma.
 19. The method of claim 18, wherein the cancer is advanced melanoma.
 20. The method of claim 18, wherein the cancer is metastatic melanoma.
 21. The method of claim 18, wherein the cancer is stage III or IV melanoma.
 22. The method of claim 21, wherein the cancer is unresectable stage III or IV melanoma.
 23. The method of claim 1-22, wherein determining the likelihood of clinical response is based on the gene expression level and at least one additional factor.
 24. The method claim 23, wherein the at least one additional factor is selected from baseline serum LDH level and disease stage.
 25. The method claim 24, wherein the at least one additional factor is baseline serum LDH level.
 26. The method of any one of claims 1-25, wherein the subject is not being treated with the immunotherapeutic agent at the time the likelihood of clinical response of the subject is determined.
 27. A method of predicting likelihood of clinical response of a subject having cancer o treatment with an immunotherapeutic agent, comprising: obtaining a blood sample from the subject before the treatment, determining expression level of at least one gene in the blood sample, wherein the at least one gene is selected from a first group of genes as listed in Table 2 and a second group of genes as listed in Table 3; determining likelihood of clinical response to the treatment based on the expression level of the at least one gene in the blood sample, wherein the expression level of the at least one gene selected from the first group of genes is positively correlated with the likelihood of clinical response, and wherein the expression level of the at least one gene selected from the second group of genes is negatively correlated with the likelihood of clinical response.
 28. The method claim 27, wherein the at least one gene is selected from IL2RB, KLRK1, G3BP, PPP1R16B, CLIC3, PRF1, SPON2, HOP, GNLY, TMEM161A, PRKCH, RUNX3, EOMES, SLC25A5, GZMB, IMP3, and ZAP70, wherein the expression level of the at least one gene is positively correlated with the likelihood of clinical response.
 29. The method claim 27, wherein the at least one gene is selected from ASGR1, ASGR2, CENTA2, PGLS, MAPBPIP, STX10, C16ORF68, and RAB31, wherein the expression level of the at least one gene is negatively correlated with the likelihood of clinical response.
 30. The method claim 27, wherein the expression level of at least two genes in the blood sample is determined, and wherein determining the likelihood of clinical response is based on the expression level of the at least two genes in the blood sample.
 31. The method of claim 30, wherein a first gene of the at least two genes is selected from the first group of genes as listed in Table 2, and a second gene of the at least two genes is selected from the second group of genes as listed in Table
 3. 32. The method of claim 31, wherein the first gene is selected from IL2RB, KLRK1, G3BP, PPP1R16B, CLIC3, PRF1, SPON2, HOP, GNLY, TMEM161A, PRKCH, RUNX3, EOMES, SLC25A5, GZMB, IMP3, and ZAP70.
 33. The method of claim 31, wherein the second gene is selected from ASGR1, ASGR2, CENTA2, PGLS, MAPBPIP, STX10, C16ORF68, and RAB31.
 34. The method of claim 31, wherein the first gene is IL2RB and the second gene is selected from ASGR1 and ASGR2.
 35. The method of claim 34, wherein the first gene is IL2RB and the second gene is ASGR2.
 36. The method of claims 30, wherein determining the likelihood of clinical response comprises subjecting the expression level of the at least two genes to a formula to calculate a score, wherein the formula is pre-determined by statistical analysis of (a) clinical response of a plurality of patients having the cancer to treatment with the immunotherapeutic agent and (b) the expression level of the at least two genes in pre-treatment blood samples from the plurality of patients.
 37. The method of claim 36, wherein a first gene of the at least two genes is selected from the first group of genes as listed in Table 2, and a second gene of the at least two genes is selected from the second group of genes as listed in Table 3, wherein the formula for calculating the score is Score=−C ₁ *X _(first gene) +C ₂ *X _(second gene), wherein X_(first gene) and X_(second gene) are normalized mRNA expression level of the first and the second gene, respectively, and C1 and C2 are each, independently, a number ranging from 0.01 to 3, and wherein the score is negatively correlated with the likelihood of clinical response.
 38. The method of claim 37, wherein C₁ ranges from 0.1 to 2, and C₂ ranges from 0.1 to 1.5.
 39. The method of claim 38, wherein the first gene is IL2RB, and the second gene is ASGR2, and wherein C₁ ranges from 0.2 to 1.5, and C₂ ranges from 0.1 to
 1. 40. The method of claim 32, wherein the score is compared to a predetermined threshold, wherein a score that is lesser than the threshold is indicative of high likelihood of clinical response, and a score that is greater than the threshold is indicative of low likelihood of clinical response.
 41. The method of any of claims 27-40, wherein the expression level of the at least one gene is measured by at least one method selected from microarray, quantitative polymerase chain reaction (qPCR), and flow cytometry.
 42. The method of any one of claims 27-41, wherein the immunotherapeutic agent is an anti-CTLA4 antibody.
 43. The method of claim 42, wherein the anti-CTLA4 antibody is ipilimumab.
 44. The method of any one of claims 27-43, wherein the cancer is selected from melanoma, prostate cancer, lung cancer, ovarian cancer, gastric cancer, and glioblastoma.
 45. The method of claim 44, wherein the cancer is advanced melanoma.
 46. The method of claim 44, wherein the cancer is metastatic melanoma.
 47. The method of claim 44, wherein the cancer is stage III or IV melanoma.
 48. The method of claim 47, wherein the cancer is unresectable stage III or IV melanoma.
 49. The method of claim 27-48, wherein determining the likelihood of clinical response is based on the gene expression level and at least one additional factor.
 50. The method claim 49, wherein the at least one additional factor is selected from baseline serum LDH level and disease stage.
 51. The method claim 50, wherein the at least one additional factor is baseline serum LDH level.
 52. The method of any one of claims 27-51, wherein the subject is not being treated with the immunotherapeutic agent at the time the likelihood of clinical response of the subject is determined.
 53. A method for treating a subject having melanoma with an ipilimumab, comprising determining expression level of at least one gene in a blood sample obtained from the subject, wherein the at least one gene is selected from a first group of genes as listed in Table 2 and a second group of genes as listed in Table 3; determining likelihood of clinical response to the treatment based on the expression level of the at least one gene in the blood sample, wherein the expression level of the at least one gene selected from the first group of genes is positively correlated with the likelihood of clinical response, and wherein the expression level of the at least one gene selected from the second group of genes is negatively correlated with the likelihood of clinical response; and administering to the subject a therapeutically effective amount of the ipilimumab for treating melanoma.
 54. A method for treating a subject having melanoma with an ipilimumab, comprising determining expression level of at least one gene in a blood sample obtained from the subject, wherein the at least one gene is selected from a first group of genes as listed in Table 2 and a second group of genes as listed in Table 3; determining likelihood of clinical response to the treatment based on the expression level of the at least one gene in the blood sample, wherein the expression level of the at least one gene selected from the first group of genes is positively correlated with the likelihood of clinical response, and wherein the expression level of the at least one gene selected from the second group of genes is negatively correlated with the likelihood of clinical response; and administering to the subject a therapeutically effective amount of the ipilimumab for treating melanoma if the likelihood of clinical response is higher than a predetermined value.
 55. A method for determining whether to treat a subject having cancer with a immunotherapeutic agent, comprising obtaining a blood sample from the subject, determining expression level of at least one gene in a blood sample obtained from the subject, wherein the at least one gene is selected from a first group of genes as listed in Table 2 and a second group of genes as listed in Table 3; determining likelihood of clinical response to the treatment based on the expression level of the at least one gene in the blood sample, wherein the expression level of the at least one gene selected from the first group of genes is positively correlated with the likelihood of clinical response, and wherein the expression level of the at least one gene selected from the second group of genes is negatively correlated with the likelihood of clinical response; and determining whether to treat the subject having cancer with the immunotherapeutic agent based on the likelihood of clinical response.
 56. A method for determining whether to treat a subject having melanoma with ipilimumab, comprising obtaining a blood sample from the subject, determining expression level of at least one gene in a blood sample obtained from the subject, wherein the at least one gene is selected from a first group of genes as listed in Table 2 and a second group of genes as listed in Table 3; determining likelihood of clinical response to the treatment based on the expression level of the at least one gene in the blood sample, wherein the expression level of the at least one gene selected from the first group of genes is positively correlated with the likelihood of clinical response, and wherein the expression level of the at least one gene selected from the second group of genes is negatively correlated with the likelihood of clinical response; and determining whether to treat the subject having cancer with ipilimumab based on the likelihood of clinical response.
 57. A kit comprising one or more reagents for determining expression level of at least one gene in a blood sample, wherein the at least one gene is selected from a first group of genes as listed in Table 2 and a second group of genes as listed in Table
 3. 58. The kit of claim 57, wherein the one or more reagents are used to determine mRNA expression level of the at least one gene.
 59. The kit of claim 57, comprising at least one polynucleotide capable of specifically hybridizing to the at least one gene.
 60. The method claim 57, wherein the at least one gene is selected from IL2RB, KLRK1, G3BP, PPP1R16B, CLIC3, PRF1, SPON2, HOP, GNLY, TMEM161A, PRKCH, RUNX3, EOMES, SLC25A5, GZMB, IMP3, and ZAP70.
 61. The method claim 57, wherein the at least one gene is selected from ASGR1, ASGR2, CENTA2, PGLS, MAPBPIP, STX10, C16ORF68, and RAB31.
 62. The method claim 57, wherein the kit comprises one or more reagents for determining expression level of at least two genes in the blood sample.
 63. The method of claim 62, wherein a first gene of the at least two genes is selected from the first group of genes as listed in Table 2, and a second gene of the at least two genes is selected from the second group of genes as listed in Table
 3. 64. The method of claim 63, wherein the first gene is selected from IL2RB, KLRK1, G3BP, PPP1R16B, CLIC3, PRF1, SPON2, HOP, GNLY, TMEM161A, PRKCH, RUNX3, EOMES, SLC25A5, GZMB, IMP3, and ZAP70.
 65. The method of claim 63, wherein the second gene is selected from ASGR1, ASGR2, CENTA2, PGLS, MAPBPIP, STX10, C16ORF68, and RAB31.
 66. The method of claim 63, wherein the first gene is IL2RB and the second gene is selected from ASGR1 and ASGR2.
 67. The method of claim 66, wherein the first gene is IL2RB and the second gene is ASGR2.
 68. A method for treating a subject having cancer with an immunotherapeutic agent, comprising determining expression levels of a first gene and a second gene in a blood sample obtained from the subject, wherein the first gene is IL2RB and a second gene is selected from ASGR1 and ASGR2; determining likelihood of longer overall survival of the subject following the treatment based on the expression levels of the first gene and the second gene in the blood sample, wherein the expression levels of the first gene and the second gene are used to calculate a score according to formula: Score=−C ₁ *X _(first gene) +C ₂ *X _(second gene), wherein X_(first gene) and X_(second gene) are normalized mRNA expression levels of the first and the second gene, respectively, and C1 and C2 are each, independently, a number ranging from 0.01 to 3, wherein the score is negatively correlated with the likelihood of longer overall survival; administering to the subject a therapeutically effective amount of the immunotherapeutic agent for treating the cancer.
 69. The method of claim 68, wherein C₁ ranges from 0.1 to 2, and C₂ ranges from 0.1 to 1.5.
 70. The method of claim 68, wherein the first gene is IL2RB, and the second gene is ASGR2, and wherein C₁ ranges from 0.2 to 1.5, and C₂ ranges from 0.1 to
 1. 71. The method of claim 68, wherein the score is compared to a predetermined threshold, wherein a score that is lower than the threshold is indicative of high likelihood of longer overall survival, and a score that is higher than the threshold is indicative of low likelihood of longer overall survival.
 72. The method of any of claims 68-71, wherein the expression level of the at least one gene is measured by at least one method selected from microarray and quantitative polymerase chain reaction (qPCR).
 73. The method of any one of claims 68-72, wherein the immunotherapeutic agent is an anti-CTLA4 antibody.
 74. The method of claim 73, wherein the anti-CTLA4 antibody is ipilimumab.
 75. The method of any one of claims 68-74, wherein the cancer is selected from melanoma, prostate cancer, lung cancer, ovarian cancer, gastric cancer, and glioblastoma.
 76. The method of claim 75, wherein the cancer is advanced melanoma.
 77. The method of claim 75, wherein the cancer is metastatic melanoma.
 78. The method of claim 75, wherein the cancer is stage III or IV melanoma.
 79. The method of claim 78, wherein the cancer is unresectable stage III or IV melanoma.
 80. The method of claim 68-79, wherein determining the likelihood of clinical response is based on the gene expression level and at least one additional factor.
 81. The method claim 80, wherein the at least one additional factor is selected from baseline serum LDH level and disease stage.
 82. The method claim 80, wherein the at least one additional factor is baseline serum LDH level.
 83. The method of any one of claims 68-82, wherein the subject is not being treated with the immunotherapeutic agent at the time the likelihood of clinical response of the subject is determined.
 84. A method of predicting likelihood of longer overall survival of a subject having cancer to treatment with an immunotherapeutic agent, comprising: obtaining a blood sample from the subject before the treatment, determining expression levels of a first gene and a second gene in the blood sample obtained from the subject, wherein the first gene is IL2RB and a second gene is selected from ASGR1 and ASGR2; determining likelihood of longer overall survival of the subject following the treatment based on the expression levels of the first gene and the second gene in the blood sample, wherein the expression levels of the first gene and the second gene are used to calculate a score according to formula: Score=−C ₁ *X _(first gene) +C ₂ *X _(second gene), wherein X_(first gene) and X_(second gene) are normalized mRNA expression levels of the first and the second gene, respectively, and C1 and C2 are each, independently, a number ranging from 0.01 to 3, wherein the score is negatively correlated with the likelihood of longer overall survival.
 85. The method of claim 84, wherein C₁ ranges from 0.1 to 2, and C₂ ranges from 0.1 to 1.5.
 86. The method of claim 84, wherein the first gene is IL2RB, and the second gene is ASGR2, and wherein C₁ ranges from 0.2 to 1.5, and C₂ ranges from 0.1 to
 1. 87. The method of claim 84, wherein the score is compared to a predetermined threshold, wherein a score that is lower than the threshold is indicative of high likelihood of longer overall survival, and a score that is higher than the threshold is indicative of low likelihood of longer overall survival.
 88. The method of any of claims 84-87, wherein the expression level of the at least one gene is measured by at least one method selected from microarray and quantitative polymerase chain reaction (qPCR).
 89. The method of any one of claims 84-88, wherein the immunotherapeutic agent is an anti-CTLA4 antibody.
 90. The method of claim 89, wherein the anti-CTLA4 antibody is ipilimumab.
 91. The method of any one of claims 84-90, wherein the cancer is selected from melanoma, prostate cancer, lung cancer, ovarian cancer, gastric cancer, and glioblastoma.
 92. The method of claim 91, wherein the cancer is advanced melanoma.
 93. The method of claim 91, wherein the cancer is metastatic melanoma.
 94. The method of claim 91, wherein the cancer is stage III or IV melanoma.
 95. The method of claim 94, wherein the cancer is unresectable stage III or IV melanoma.
 96. The method of claim 84-95, wherein determining the likelihood of clinical response is based on the gene expression level and at least one additional factor.
 97. The method claim 96, wherein the at least one additional factor is selected from baseline serum LDH level and disease stage.
 98. The method claim 96, wherein the at least one additional factor is baseline serum LDH level.
 99. The method of any one of claims 84-98, wherein the subject is not being treated with the immunotherapeutic agent at the time the likelihood of clinical response of the subject is determined. 